Trans Phys Block 1

Total Body Water (TBW)

60% of body weight in males, 50% in females

ECF Volume

1/3 of total body water

ICF Volume

2/3 of total body water

Plasma Volume

20% of extracellular fluid

Interstitial Fluid

80% of extracellular fluid

Isotonic Fluid Loss

Decreases ECF volume only

Hypotonic Fluid Loss

Increases ECF osmolarity and decreases ICF volume

Hypertonic Fluid Gain

Increases ECF osmolarity and decreases ICF volume

Hypotonic Fluid Gain

Decreases osmolarity and increases ICF volume

AVP (Vasopressin)

Hormone that increases water reabsorption in the collecting duct

AQP-2

Water channel inserted into apical membrane by AVP

V2 Receptor

Gs-coupled receptor increasing cAMP and PKA for water reabsorption

V1 Receptor

Gq-coupled receptor causing vasoconstriction

Hyponatremia Symptoms

Nausea, confusion, gait disturbance, lethargy

Brain Response to Hyponatremia

Loss of electrolytes and organic osmolytes to reduce swelling

Osmotic Demyelination

Caused by rapid correction of chronic hyponatremia

Brain Response to Hypernatremia

Accumulation of electrolytes and osmolytes to prevent shrinkage

Cerebral Edema

Caused by rapid correction of chronic hypernatremia

Central Diabetes Insipidus

Decreased or absent AVP secretion

Nephrogenic Diabetes Insipidus

Kidney unresponsive to AVP

SIADH

Excess AVP causing concentrated urine and hyponatremia

Water Deprivation Test

Differentiates central vs nephrogenic DI

Insulin Resistance

Decreased biological response of tissues to insulin

Compensated Insulin Resistance

Normal glucose maintained by increased insulin secretion

Uncompensated Insulin Resistance

Hyperglycemia due to beta-cell failure

PPARγ

Nuclear receptor regulating adipogenesis and triglyceride synthesis

TNF-α

Cytokine that decreases PPARγ and promotes insulin resistance

MCP-1

Macrophage chemoattractant released by stressed adipocytes

Ectopic Lipid

Lipid stored in liver, muscle, or pancreas

FFA Effects

Increase gluconeogenesis and decrease glucose uptake

Metformin

Suppresses hepatic gluconeogenesis

Sulfonylureas

Increase insulin secretion from pancreatic beta cells

GLP-1 Agonists

Increase insulin secretion and promote beta-cell survival

TZDs

Activate PPARγ to improve insulin sensitivity

Insulin Receptor

Receptor tyrosine kinase initiating PI3K/AKT signaling

PI3K

Converts PIP2 to PIP3

PDK1

Activates PKB/Akt

PKB/Akt

Promotes GLUT4 translocation to the cell surface

Catecholamines

Stimulate lipolysis via beta-adrenergic receptors

Insulin and Lipolysis

Insulin suppresses lipolysis

LEMS

Autoimmune attack on presynaptic P/Q-type voltage-gated calcium channels

MG

Autoimmune attack on postsynaptic nicotinic acetylcholine receptors

3,4-DAP

Blocks presynaptic K+ channels to increase ACh release in LEMS

Pyridostigmine

Reversible acetylcholinesterase inhibitor used in MG

Synaptotagmin

Calcium sensor triggering synaptic vesicle fusion

SNARE Complex

Synaptobrevin, SNAP-25, and syntaxin

DHPR

Voltage sensor in T-tubule activating RyR1

RyR1

Releases calcium from sarcoplasmic reticulum

Synaptic Facilitation

Caused by residual presynaptic calcium

Synaptic Depression

Caused by vesicle depletion

Acetylcholinesterase

Breaks acetylcholine into acetate and choline

Chest CT in LEMS

Screens for small-cell lung carcinoma

Post-Exercise Facilitation

Increased CMAP amplitude due to residual calcium in LEMS

Decremental Response

EMG finding characteristic of MG

CMAP Amplitude in LEMS

Low at baseline, increases >100% with high-frequency stimulation

Autonomic Symptoms in LEMS

Orthostatic hypotension, dry mouth, constipation

Voltage-Gated Calcium Channels

Required for presynaptic ACh release

SNARE Proteins

Mediate vesicle docking, priming, and fusion

Synaptophysin

Regulates vesicle trafficking and recycling

Rab3

Vesicle trafficking protein

ACh Breakdown

Terminates neuromuscular signaling

Nicotinic ACh Receptor

Ligand-gated ion channel on muscle endplate

Endplate Potential

Depolarization caused by Na+ influx through nAChRs

Muscle Action Potential

Triggered when EPP reaches threshold

T-Tubule Depolarization

Activates DHPR

Calcium-Induced Calcium Release

DHPR mechanically activates RyR1

Troponin C

Binds calcium to initiate muscle contraction

Tropomyosin Shift

Exposes myosin-binding sites on actin

Cross-Bridge Cycling

Mechanism of muscle contraction

Residual Calcium

Mechanism of synaptic facilitation

Readily Releasable Vesicle Pool

Depleted during synaptic depression

ACh Recycling

Choline reuptake into presynaptic terminal

Small-Cell Lung Cancer

Most common malignancy associated with LEMS

Anti-VGCC Antibodies

Diagnostic for LEMS

Anti-AChR Antibodies

Diagnostic for MG

Orthostatic Hypotension

Autonomic dysfunction seen in LEMS

Voltage-Gated Sodium Channels

Propagate muscle action potential

Hypertonic Saline Infusion

Increases ECF osmolarity and decreases ICF volume

Isotonic Saline Infusion

Increases ECF volume only

Sweat Loss

Hypotonic fluid loss increasing ECF osmolarity

Diarrhea

Isotonic fluid loss decreasing ECF volume

Vomiting

Isotonic fluid loss decreasing ECF volume

Water Intoxication

Hypotonic fluid gain increasing ICF volume

Ocean Water Ingestion

Hypertonic gain increasing ECF osmolarity

Osmoreceptors

Sense plasma osmolarity and regulate AVP release

Set Point for AVP Release

Approximately 290 mOsm/kg

Mechanosensitive Channels

Activated by cell shrinkage to trigger AVP release

AQP-3 and AQP-4

Basolateral water channels in collecting duct

Long-Term AVP Effect

Increased transcription of AQP-2

Short-Term AVP Effect

Insertion of AQP-2 into apical membrane

Hypernatremia Symptoms

Lethargy, weakness, irritability

Hypovolemia

Stimulates non-osmotic AVP release

Effective Circulating Volume

Regulates V1 receptor-mediated vasoconstriction