BME2010 Physiology Prelim 1

Levels of Organization in Human Body

Cell → Tissue → Organ → Organ System

ATP

Breaking this down is where cells get the energy needed for ‘work’

ATP + H₂O → ADP + Energy + P^-

Glucose Metabolism Equation

C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + (Energy)

Glucose Oxidation

Oxidizing glucose creates energy and heat, which is coupled to create ATP from ADP+P ion

Two Types of Metabolic Reactions

Anabolic reactions and catabolic reactions

Anabolic Reactions

Growth reactions, requires energy. Often involves condensation + reduction.

ex. building ATP from ADP

Catabolic Reactions

Breakdown reactions, release energy. Often involves hydrolysis + oxidation.

ex. breaking down ATP to ADP

Glucose Metabolism

Central reaction of energy metabolism, with each glucose needing 6O₂
Energy from 1 mole of glucose ΔE = –686 kcal/mole

Moles of ATP From One Mole of Glucose

32 ATP

Stages of Glucose Oxidation

Glycolysis → Linking Step → Krebs Cycle → Oxidative Phosphorylation

Glycolysis

Occurs in the cytoplasm, uses 2 ATP, creates 4 → Net 2
In: Glucose, 2NAD⁺, 2ADP+2Pi
Out: 2 Pyruvate, 2 (NADH + H⁺), 2 ATP

Linking Step

Converts pyruvate (from Glycolysis) to Acetyl CoA, NADH + H⁺, and CO₂. Occurs in the mitochondrial matrix

Initial Substrate for Krebs Cycle

Acetyl CoA

Krebs Cycle (Citric Acid Cycle, Tricarboxylic Acid Cycle)

Cyclic metabolic pathway that cycles through 8 organic molecules. Occurs in the mitochondrial matrix.

In: Acetyl CoA, 3H₂O
Out: 3 NADH, 1 FADH, 2CO₂, 1 ATP

Two Sections of Oxidative Phosphorylation

Electron transport chain and chemiosmotic coupling

Electron Transport Chain (ETC)

Electrons released from carriers (NADH and FADH₂) and are passed down through reversible reduction reactions, releasing energy in the process. O₂ is the last acceptor.

Chemiosmotic Coupling

Couples ETC to ATP synthesis by creating a proton gradient which flows through and spins the ATP synthase molecule.

ATP Per NADH → NAD+

2-3 (avg 2.5)

ATP Per FADH₂ → FAD

1-2 (avg 1.5)

ATP Generated Per Step (Glucose Oxidation)

Glycolysis: 2
Linking Step: 0
Krebs Cycle: 2
Oxidative Phosphorylation: 28

Precise numbers of ATP generated will vary based on cell type and environment.

Aerobic Conditions

Tissue O₂ supply = tissue metabolic demand

Anaerobic Conditions

Tissue O₂ supply ≠ tissue metabolic demand

Glucose Catabolism during Low Oxygen Supply

Only Glycolysis, however an additional step to reuse the NADH. Converting Pyruvate to Lactate converts NADH→NAD+ via lactate dehydrogenase so it can be used again.

Disadvantages of Anaerobic Glucose Catabolism

• ATP production highly inefficient, only 2 ATP

• Lactate buildup creates acidification of tissue

Anaerobic → Aerobic Glucose Metabolism

Lactose dehydrogenase reverses the reaction, converting lactate back into pyruvate which enters the Krebs Cycles.

Body’s Primary Energy Source

Glucose

Glycogen

A long polymer of glucose

Glycogenesis

Creating new glycogen from glucose. Happens when glucose is abundant in the body and needs to be stored.

Glycogenolysis

Breaking down glycogen into glucose. Happens when glucose is low in the body and needs to be created.

Alternate Metabolic Molecules

Proteins and triglycerides

Triglycerides

Composed of a glycerol molecule and 3 fatty acids

Fatty Acids

Multi carbon compounds found in triglycerides and lipases

Lipolysis (Triglyceride Metabolism)

Glycerol enters glycolysis, fatty acids are converted to Acetyl CoA (for Krebs Cycle) and Coenzyme 2H (for Oxidative Phosphorylation)

Acetyl CoA Accumulation

Can lead to ketone production

Protein Metabolism

Proteins → amino acids → keto acids → pyruvate, acetyl CoA, Krebs Cycle

Proteolysis

Converts proteins to amino acids. First step in protein metabolism.

Deamination

Removal of the amino group (—NH₂) from amino acids, resulting in a keto acid and ammonia (NH₃, later converted to urea). Second step of protein metabolism.

Gluconeogenesis

Synthesis of new glucose from non carbohydrate precursors, including glycerol and amino acids. Primarily occurs in liver.

Branches of the Nervous System

Central Nervous System (CNS) and Peripheral Nervous System (PNS)

Central Nervous System (CNS)

Includes spinal cord and brain

Peripheral Nervous System (PNS)

Includes afferent neurons and efferent neurons

Afferent Neuron

Receptor → CNS

Efferent Neurons

CNS → effector

Cells in the Nervous System

Neurons and glial cells

Neuron Structure

• Cell body (w/ nucleus)

• Dendrites to detect stimuli

• Axons to conduct action potentials

• Axon hillock to integrate potentials

• Synaptic knobs (axon terminals) for neurotransmitters

Types of ion channels

Ligand gated, mechanically gated, always open, and voltage gated.

Structural Classifications of Neurons

Bipolar: dendrites on both sides, cell body in middle

Pseudo-unipolar: dendrites on both sides, cell body outside of central axon

Multipolar: cell body inside dendrites on one side, dendrites after axon on other side

Types of Afferent Neurons

• Somatic + special sensory: skeletal muscle or skin to CNS

• Visceral: visceral organ to CNS

Types of Efferent Neurons

• Somatic (motor): provide voluntary control of muscle tissue

• Autonomic: involuntary control of internal organs

Interneurons

Neurons entirely contained within the CNS

Glial Cells

Provide structural integrity to the nervous system (glia in Latin means “glue”)

Types of Glial Cells

CNS: Astrocytes, Microglia, Oligodendrocytes

PNS: Schwann cells

Schwann Cells

Wraps around axons in PNS like burrito, forming myelin sheath.

Nodes of Ranvier

Exposed sections of the axon (not covered by myelin shealth)

Multiple Sclerosis (MS)

A disease causing the myelin sheath to get damaged resulting in exposed axon fibers.

Cellular Fluids

ICF: Intracellular fluid

ECF: Extracellular fluid

Resting Membrane Potential

Voltage potential difference across cell membranes at rest (all cells have a different resting potential) V_ICF - V_ECF

ECF ICF Ion Concentrations

Sodium more concentrated outside the cell

Potassium more concentrated inside the cell

Resting Potential of an Ion

The resting potential of an ion is when the concentration gradient driving the ion out and the electrical pull driving back in are equal.

Potassium Equilibrium Potential

E_K = -94 mV

Sodium Equilibrium Potential

E_Na = +60 mV

Neuron Resting Potential Control

Neurons have open potassium and open sodium channels, but have more potassium channels. An Na+/K+ pump maintains gradient.

Neuron Membrane Potential Balance

Membrane is about 25x more permeable to potassium, resulting in the resting membrane potential being much closer to E_K than E_Na

Neuron Resting Membrane Potential

-70 mV

Neuron Electrical Stimulation

Neurons can be stimulated by opening and closing of gated Na+/K+ channels in response to stimuli, affecting the permeability.

Depolarization

Becoming less polarized, generally less negative

Repolarization

Returning to resting potential after depolarization

Hyperpolarization

Becoming more negative (more polarized)

Types of Electrical Signals

Graded potentials and action potentials

Graded Potentials

• Small electrical signals

• Short distance

• Decremental (size of polarization changes w/ distance)

Action Potentials

• Large electrical signals

• Long distance

• Non-decremental (do no change amplitude over distance)

Neural Integration

A single neuron receives communication from multiple neurons which are combined at the Axon Hillock, which integrates all graded potentials.

Temporal Summation

Stimulus is applied from the same place in rapid succession

Spatial Summation

Stimuli from multiple different sources occur close in time

Action Potential Threshold

The minimum necessary depolarization to induce an action potential

Action Potential Process

Stimulus causes depolarization → Action potential reached → Rapid depolarization occurs → Rapid repolarization occurs

Excitatory Graded Potential

Depolarizing potential, brings membrane potential closer to threshold

Inhibitory Graded Potential

Hyperpolarizing potential, takes membrane potential away from threshold

Phases of Action Potential

(Phase 1) Rapid Depolarization

(Phase 2) Repolarization

(Phase 3) Hyperpolarization

(Phase 1) Rapid Depolarization

Dramatic increase in sodium permeability, sodium moves into the cell and it approaches V_m ~ E_Na

(Phase 2) Repolarization

Reduced sodium permeability, increased potassium permeability, ion balance begins to form again V_m ~ Resting Potential

(Phase 3) Hyperpolarization

Potassium permeability remains elevated, overshooting as potassium moves out of the cell V_m ~ E_K

“All or None” Action Potential

Membrane can either be depolarized or not depolarized. There is no concept of strength or variable power of action potentials.

Threshold Depolarization

Minimum amount necessary to induce regenerative mechanism for opening sodium channels

Subthreshold Depolarization

Below threshold, may open some sodium channels but not enough to reach the threshold.

Suprathreshold Depolarization

Greater than the threshold, causes action potential

Dual Gated Na+ Channels

Consists of the activation gate and inactivation gate

Dual Gated Na+ Behavior

Depolarization → activation gate opens (inactivation already open) → Na+ flows through → 1ms later, inactivation gate closes → Inactivation can’t open until membrane potential returns to resting state

Refractory period

Period of reduced membrane excitability (action potential difficult or impossible). Includes relative and absolute refractory period

Absolute Refractory Period

Na+ inactivation gates are closed, meaning Na+ is physically incapable of entering so a new AP cannot be generated. Starts at threshold reached, ends at repolarizing back to threshold.

Relative Refractory Period

Na+ gated channels are open at the same time as potassium gated. Second action potential can be generated, but due to hyperpolarization, it takes considerably more effort.

Frequency Coding

To send more intense stimuli via binary AP, many AP are sent in rapid succession. Like PWM

Generating Series of APs

A suprathreshold stimulus can general APs quicker because it will reach the threshold immediately, allowing it to skip the relative refractory period by overpowering the hyperpolarization.

AP Propagation

After firing, AP is propagated down axon without decrement by a wave-like depolarization.

Section depolarizes → ions flow away from section, causing them to depolarize → because previous section is in refractory, only goes forward → new forward section depolarizes.

Saltatory Condiction

Conduction of axon potential via nodes of Ranvier in myelinated axons. “Jumps” from uncovered section to uncovered section

Myelinated Axon Speed

Myelinated axons conduct charge faster because the signal travels without constant ion transfer which is slow compared to electrical signal movement.

Synapse

Functional association of neuron with another neuron or effector organ

Synaptic Cleft

The space between the presynaptic neuron and postsynaptic neuron

Synaptic Communication

1. Action potential reaches axon → voltage gated Ca²⁺ opens allowing entry

2. Ca²⁺ releases neurotransmitters, more Ca²⁺ = more neurotransmitters

3. Neurotransmitter moves to postsynaptic neuron causing channels to open

Neurotransmitter in Postsynaptic Neuron

Neurotransmitter opens or closes ion channels. Depending on type, can cause depolarization or hyperpolarization.