ANS – Sympathetic vs Parasympathetic Sleep (REM vs NREM) EEG waves CSF formation & circulation Hypothalamus functions Pituitary gland Thyroid hormones Insulin & glucagon Adrenal cortex hormones Calcium homeostasis (PTH, Calcitonin, Vitamin D) Calcium (imp) EEG Sleep Thyroid (imp)

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Physiology Study Notes - Complete Review

1. ANS - Sympathetic vs Parasympathetic

Sympathetic and Parasympathetic ANS diagram

Origin (Outflow)

Feature	Sympathetic	Parasympathetic
Outflow	Thoracolumbar (T1-L2)	Craniosacral (CN III, VII, IX, X + S2-S4)
Preganglionic fiber	Short	Long
Postganglionic fiber	Long	Short
Ganglion location	Paravertebral / prevertebral (far from organ)	Terminal ganglia (in/near organ wall)
Neurotransmitter (pre)	ACh (nicotinic)	ACh (nicotinic)
Neurotransmitter (post)	NE (adrenergic)	ACh (muscarinic)

Exception: Adrenal medulla gets direct preganglionic sympathetic fibers (no postganglionic neuron); releases EPI + NE directly into blood.

Functional Effects (Organ by Organ)

Organ	Sympathetic ("fight or flight")	Parasympathetic ("rest & digest")
Heart rate	Increases (β1)	Decreases (M2)
Contractility	Increases (β1)	Slight decrease
Bronchi	Dilates (β2)	Constricts
GI motility	Decreases (α2, β2)	Increases
GI sphincters	Contracts (closes)	Relaxes
Pupils	Dilates - mydriasis (α1)	Constricts - miosis (M3)
Salivary glands	Thick, viscous saliva (α1)	Watery, profuse saliva
Bladder detrusor	Relaxes (β2)	Contracts (M3)
Bladder sphincter	Contracts (α1)	Relaxes
Blood vessels (skin, viscera)	Constricts (α1)	Minimal direct effect
Sweat glands	Activates (cholinergic sympathetic - muscarinic)	-
Adrenal medulla	EPI/NE secretion	-
Liver	Glycogenolysis (β2, α1)	-
Eye (ciliary muscle)	Relaxes (β2) - far vision	Contracts (M3) - near vision

Key receptors: α1 (vasoconstriction, pupil dilation), α2 (presynaptic inhibition), β1 (heart), β2 (bronchi, blood vessels), M2 (heart), M3 (smooth muscle, glands).

Histology: A Text and Atlas, p. 988-989

2. Sleep - REM vs NREM

NREM Sleep (Non-Rapid Eye Movement)

NREM has 4 stages (or 3 in newer classification merging stages 3+4):

Stage	EEG	Features
N1 (Stage 1)	Theta waves (4-7 Hz)	Lightest sleep; hypnic jerks; easily awakened
N2 (Stage 2)	Sleep spindles (8-14 Hz) + K complexes	True sleep begins; ~50% of total sleep
N3 (Stage 3)	Delta waves (<4 Hz, >20%)	Slow-wave sleep (SWS) / deep sleep
N4 (Stage 4)	Delta waves (>50%)	Deepest; GH release; sleepwalking/night terrors

(Note: Modern AASM classification merges N3+N4 into a single N3 stage)

REM Sleep (Rapid Eye Movement)

EEG resembles waking state - low voltage, high frequency (beta-like, "desynchronized")
Rapid eye movements, muscle atonia (paralysis of voluntary muscles via glycine/GABA inhibition)
Most vivid dreaming occurs here
Occurs in cycles of ~90 minutes; first REM period is short (~10 min), lengthens toward morning
Penile/clitoral tumescence (physiological)
Increased brain O2 consumption

Sleep Architecture

Total sleep time: ~7-9 hours in adults
Cycles: 4-6 per night, each ~90 minutes
Early night: More NREM (deep, slow-wave)
Late night: More REM
REM deprivation → REM rebound on recovery nights

Key Neurochemistry

State	Dominant neurotransmitters
Wake	ACh (high), NE (high), Serotonin (high), Histamine (high)
NREM	All aminergic systems decrease; GABA increases
REM	ACh (high - REM-on); NE + Serotonin virtually silent (REM-off)

Adenosine builds up during wakefulness → sleep pressure (caffeine blocks adenosine receptors)
SCN (suprachiasmatic nucleus) controls circadian rhythm; melatonin from pineal gland promotes sleep onset

3. EEG Waves ⭐ (Important)

Normal EEG showing alpha and beta rhythms

A normal EEG. First seconds show alpha activity (8-13 Hz), largest occipital. At the arrows, subject opened eyes - alpha suppressed, replaced by faster beta rhythms.

EEG Wave Summary Table

Wave	Frequency	Amplitude	State/Association
Delta (δ)	< 4 Hz	High	Deep NREM sleep (N3/N4); coma; infants; abnormal in awake adults
Theta (θ)	4-7 Hz	Medium	Light sleep (N1); drowsiness; emotional states; normal in children
Alpha (α)	8-13 Hz	Medium	Relaxed, awake, eyes closed; largest over occipital cortex; disappears on eye opening
Mu (μ)	8-13 Hz	Medium	Similar to alpha; over motor/somatosensory cortex; disappears with motor activity
Beta (β)	15-30 Hz	Low	Alert/active thinking; eye opening; mental activity; benzodiazepines increase beta
Gamma (γ)	30-90 Hz	Very low	Activated, attentive cortex; perception binding; cognitive processing

Sleep-Specific EEG Features

Feature	Frequency	Stage
Sleep spindles	8-14 Hz (brief bursts)	N2 (hallmark of N2)
K complexes	Nonrhythmic sharp wave + slow wave	N2 (often precedes spindles)
Delta waves	<4 Hz (large amplitude)	N3/N4 (slow-wave sleep)
Ripples	80-200 Hz (brief)	Sleep (memory consolidation)

Clinical Correlates

3 Hz spike-and-wave: Absence seizures
Triphasic waves: Hepatic encephalopathy
Burst suppression: Deep anesthesia / severe anoxic injury
Isoelectric (flat) EEG: Brain death criterion
Alpha coma: Eyes-open coma (poor prognosis)
Benzodiazepines → increase beta activity
Barbiturates → increase beta at low doses, burst suppression at high doses

Source: Neuroscience: Exploring the Brain, 5th Ed., p. 1710-1712

4. CSF Formation & Circulation

Formation

Produced mainly by choroid plexus (lateral, 3rd, 4th ventricles) - ~500 mL/day
Total volume in CNS: ~150 mL (turns over ~3x/day)
Mechanism: Active secretion (Na+/K+ ATPase driven) + ultrafiltration of plasma
Composition: Clear, colorless; low protein (~15-45 mg/dL), glucose ~60% of serum, no cells normally

Circulation Pathway

Lateral ventricles → Foramen of Monro → 3rd ventricle → Cerebral aqueduct (of Sylvius) → 4th ventricle → Foramina of Magendie (median) + Luschka (lateral) → Subarachnoid space → Arachnoid granulations → Superior sagittal sinus → Venous blood

Memory aid: "Monro-Sylvius-Magendie-Luschka"

Absorption

Primarily via arachnoid granulations (villi) into dural venous sinuses
Pressure-dependent, unidirectional flow

Clinical Points

Hydrocephalus: Obstruction of flow (communicating vs non-communicating)
Normal pressure hydrocephalus: Triad - gait apraxia, dementia, urinary incontinence ("wet, wobbly, wacky")
Lumbar puncture at L3-L4 or L4-L5 (below spinal cord termination at L1-L2)

5. Hypothalamus Functions

The hypothalamus integrates the neuroendocrine, autonomic, and behavioral systems.

Releasing/Inhibiting Hormones (for Anterior Pituitary)

Hypothalamic Hormone	Effect on Ant. Pituitary
TRH	Releases TSH, Prolactin
CRH	Releases ACTH
GnRH	Releases LH, FSH
GHRH	Releases GH
Somatostatin (SS)	Inhibits GH, TSH
Dopamine (PIH)	Inhibits Prolactin

Other Functions

Function	Region
Temperature regulation	Anterior hypothalamus (cooling); Posterior (heat conservation)
Thirst / osmolarity	Osmoreceptors → ADH release (posterior pituitary)
Hunger/Satiety	Lateral (hunger); Ventromedial (satiety - "satiety center")
Circadian rhythm	Suprachiasmatic nucleus (SCN)
Autonomic control	Posterior = sympathetic; Anterior = parasympathetic
Emotion/aggression	Limbic connections
Sleep-wake	Lateral hypothalamus (orexin/hypocretin - wakefulness)
Posterior pituitary hormones	Synthesizes ADH (vasopressin) and Oxytocin (released from posterior pituitary)

Memory aid: "TRH CRH GnRH GHRH SS DA"

6. Pituitary Gland

Anterior Pituitary (Adenohypophysis)

Derived from Rathke's pouch (oral ectoderm). Regulated by hypothalamic portal system.

Hormone	Cell Type	Primary Target	Key Effects
GH	Somatotrophs (most numerous)	Liver → IGF-1	Growth, lipolysis, anti-insulin
TSH	Thyrotrophs	Thyroid	T3/T4 synthesis & release
ACTH	Corticotrophs	Adrenal cortex	Cortisol, androgens
LH	Gonadotrophs	Gonads	Ovulation (F); testosterone (M)
FSH	Gonadotrophs	Gonads	Follicle growth (F); spermatogenesis (M)
Prolactin	Lactotrophs	Breast	Lactation; inhibits GnRH
MSH	Melanotrophs	Melanocytes	Pigmentation

Posterior Pituitary (Neurohypophysis)

Derived from neural ectoderm (diencephalon). Stores and releases hormones synthesized in hypothalamus.

Hormone	Synthesized in	Effect
ADH (Vasopressin)	Supraoptic nucleus	Water reabsorption (collecting duct V2R), vasoconstriction (V1R)
Oxytocin	Paraventricular nucleus	Uterine contraction, milk ejection, social bonding

7. Thyroid Hormones ⭐ (Important)

Synthesis Steps (in thyroid follicle)

Iodide (I-) uptake - Na+/I- symporter (NIS) on basolateral membrane - stimulated by TSH
Oxidation: I- → I2 by thyroid peroxidase (TPO) (requires H2O2)
Organification: Iodination of tyrosine residues on thyroglobulin → MIT (monoiodotyrosine) + DIT (diiodotyrosine)
Coupling (by TPO):
- MIT + DIT → T3 (triiodothyronine, more active)
- DIT + DIT → T4 (thyroxine, prohormone)
Storage: As thyroglobulin in follicular lumen (colloid) - the body's largest hormone store
Release: TSH stimulates proteolysis of thyroglobulin → T3 + T4 secreted
T4 → T3 conversion in periphery by deiodinase (T3 is 4x more potent)

Antibodies in Hashimoto thyroiditis: Anti-TPO antibodies (diagnostic)

Transport in Blood

~99.97% bound to Thyroxine-Binding Globulin (TBG), albumin, transthyretin
Only free hormone is active and participates in feedback
T4 half-life: ~7 days; T3 half-life: ~1 day

Mechanism of Action

Nuclear receptors → gene transcription
T4 deiodinated to T3 inside cells (T3 is the active form)
Increases basal metabolic rate, O2 consumption, mitochondriogenesis
Permissive for catecholamine effects (upregulates β-receptors)

Physiological Effects

System	Effect
Metabolism	↑ BMR, ↑ O2 consumption, ↑ heat production
Cardiovascular	↑ HR, ↑ CO, ↑ β-receptor sensitivity
Development	Essential for brain development (fetal) + linear growth
GI	↑ Gut motility
Bone	↑ Bone turnover
Glucose	↑ Glucose absorption and glycogenolysis

Hypothyroidism vs Hyperthyroidism

Feature	Hypothyroidism	Hyperthyroidism
TSH	↑ (primary)	↓
Metabolism	Slow - weight gain, cold intolerance	Fast - weight loss, heat intolerance
Heart	Bradycardia	Tachycardia, palpitations
GI	Constipation	Diarrhea
Skin	Dry, coarse, myxedema	Warm, moist, pretibial myxedema (Graves)
Cause	Hashimoto (anti-TPO, anti-Tg)	Graves (TSI/TSH-R antibodies)
Treatment	Levothyroxine (T4)	PTU, methimazole, β-blockers, RAI

Drug Inhibitors of Thyroid Synthesis

PTU, Methimazole: Block TPO (organification + coupling)
PTU also: Blocks peripheral T4→T3 conversion
High-dose iodide (Wolff-Chaikoff): Transiently inhibits organification
Lithium: Inhibits thyroglobulin proteolysis → blocks T3/T4 release

Source: Lippincott Illustrated Reviews Pharmacology, p. 779-781

8. Insulin & Glucagon

Insulin

Secreted by β-cells of islets of Langerhans
Stimulated by: glucose, amino acids, GIP, GLP-1, vagal (ACh), β2-adrenergic
Inhibited by: hypoglycemia, somatostatin, α2-adrenergic (sympathetic)
Mechanism: Glucose → ↑ ATP/ADP → closes K+ channels → depolarization → Ca2+ influx → insulin exocytosis

Key Actions:

Tissue	Effect
Liver	↑ Glycogen synthesis, ↑ glycolysis, ↓ gluconeogenesis, ↑ lipogenesis
Muscle	↑ Glucose uptake (GLUT4), ↑ glycogen synthesis, ↑ protein synthesis
Adipose	↑ Glucose uptake (GLUT4), ↑ lipogenesis, ↓ lipolysis
General	↓ Blood glucose, ↑ K+ uptake into cells

GLUT transporters: GLUT4 is insulin-dependent (muscle, fat). GLUT2 is in liver/pancreas (high capacity, low affinity). GLUT1 is constitutive (brain, RBCs).

Glucagon

Secreted by α-cells
Stimulated by: hypoglycemia, amino acids (especially alanine), stress, sympathetic stimulation
Inhibited by: glucose, insulin, somatostatin

Key Actions:

Tissue	Effect
Liver (primary target)	↑ Glycogenolysis, ↑ gluconeogenesis, ↑ ketogenesis
Adipose	↑ Lipolysis (↑ FFA for ketogenesis)

Acts via Gs → adenylyl cyclase → ↑ cAMP → PKA
Counter-regulatory hormones: Glucagon, cortisol, epinephrine, GH (all raise blood glucose)

9. Adrenal Cortex Hormones

Three zones - mnemonic: "GFR" = Salt (mineralocorticoids), Sugar (glucocorticoids), Sex (androgens)

Zone	Hormone	Regulator	Key Actions
Zona Glomerulosa (outer)	Aldosterone	Renin-Angiotensin, ↑ K+	Na+ retention, K+ excretion, H+ excretion (collecting duct)
Zona Fasciculata (middle)	Cortisol	ACTH (CRH)	Anti-inflammatory, gluconeogenesis, protein catabolism, immunosuppression
Zona Reticularis (inner)	DHEA, androgens	ACTH	Weak androgens; pubic/axillary hair

Cortisol Actions (Glucocorticoid)

↑ Blood glucose (gluconeogenesis, protein catabolism → amino acids)
↑ Lipolysis (central obesity with Cushing)
Anti-inflammatory: ↓ PLA2 → ↓ arachidonic acid → ↓ prostaglandins + leukotrienes
Immunosuppressive: ↓ T-cells, ↓ cytokines
↑ BP (permissive for catecholamines; some mineralocorticoid activity)
Inhibits bone formation

Aldosterone

Primary stimulus: Angiotensin II (via RAAS), hyperkalemia
Acts on principal cells of collecting duct → ↑ ENaC expression → Na+ reabsorption → water follows → volume expansion
Also ↑ H+ secretion by intercalated cells → metabolic alkalosis in excess

10. Calcium Homeostasis ⭐ (Important)

Normal serum calcium: 8.5-10.5 mg/dL (ionized: 4.5-5.6 mg/dL)

Three regulators: PTH, Calcitonin, Vitamin D

Parathyroid Hormone (PTH)

From chief cells of parathyroid glands
Stimulated by: ↓ Ca2+, ↓ Mg2+, ↓ Vitamin D
Inhibited by: ↑ Ca2+ (via CaSR - calcium sensing receptor)

Actions (remember: PTH raises Ca, lowers Phos)

Organ	PTH Effect
Bone	↑ Osteoclast activity (via osteoblast RANK-L) → Ca2+ + Phosphate released
Kidney (PCT)	↑ Ca2+ reabsorption; ↑ Phosphate excretion (phosphaturic); ↑ 1α-hydroxylase → ↑ Vitamin D activation
Kidney (DCT)	↑ Ca2+ reabsorption
GI (indirect)	Via Vitamin D → ↑ Ca2+ absorption

Net effect: ↑ serum Ca2+, ↓ serum Phosphate

Vitamin D (Calcitriol - 1,25-dihydroxycholecalciferol)

Activation pathway:

Skin: 7-dehydrocholesterol + UV → Cholecalciferol (D3)
Liver: D3 → 25-hydroxyvitamin D (storage form; measured clinically)
Kidney: 25-OH-D → 1,25(OH)2D (calcitriol - active) via 1α-hydroxylase (stimulated by PTH, ↓ Ca2+, ↓ PO4)

Actions:

↑ Intestinal Ca2+ + phosphate absorption (via calbindin)
↑ Renal Ca2+ + phosphate reabsorption
↑ Bone mineralization (at normal Ca levels); can stimulate osteoclasts in excess
Net: ↑ Ca2+, ↑ Phosphate (both)

Calcitonin

From parafollicular C-cells of thyroid
Stimulated by: ↑ Ca2+
Actions (opposes PTH):
- Inhibits osteoclasts → ↓ bone resorption
- ↑ Renal Ca2+ + phosphate excretion
Net: ↓ serum Ca2+
Physiological role is minor in adults; more important in children and during pregnancy/lactation
Clinical use: Paget's disease, hypercalcemia (short-term)

Summary Table

	PTH	Vitamin D (calcitriol)	Calcitonin
Source	Parathyroid	Kidney (activated)	Thyroid C-cells
Stimulus	↓ Ca2+	↓ Ca2+, PTH	↑ Ca2+
Serum Ca2+	↑	↑	↓
Serum Phosphate	↓	↑	↓
Bone	Resorption ↑	Mineralization ↑	Resorption ↓
GI absorption	↑ (indirect)	↑ (direct)	No effect

Clinical Points

Condition	Ca2+	PO4	PTH	Notes
Primary hyperPTH	↑	↓	↑	Kidney stones, bones, groans, psychic moans
Hypo PTH	↓	↑	↓	Tetany, Chvostek, Trousseau, prolonged QT
Vit D deficiency	↓ (or N)	↓	↑ (secondary)	Rickets (children), Osteomalacia (adults)
Malignancy	↑	Variable	↓	PTHrP or osteolytic mets
Sarcoidosis	↑	↑	↓	Macrophages produce 1α-hydroxylase
Hypercalcemia Tx	-	-	-	IV fluids, furosemide, bisphosphonates, calcitonin

Tetany features:

Chvostek sign: Tap facial nerve → facial twitch
Trousseau sign: Inflate BP cuff → carpal spasm

Sources: Neuroscience: Exploring the Brain 5th Ed. | Lippincott Illustrated Reviews Pharmacology | Histology: A Text and Atlas | Medical Physiology (Boron & Boulpaep)

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