1. Cell Membrane Structure and Function

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Questions and Answers

What aspect of cell membranes is emphasized in Cooper's text?

Membrane transport proteins

Cell membrane dynamics (correct)

Membrane lipid composition

Membrane associated diseases

Which textbook extensively discusses the pathophysiology of myocardial infarction?

The Cell: A Molecular Approach

Robbins and Cotran Pathologic Basis of Disease

Braunwald's Heart Disease (correct)

Molecular Biology of the Cell

In which publication can one find an overview of inflammatory processes in muscle injury?

Skeletal Muscle Structure, Function, and Plasticity

Molecular Biology of the Cell

The Cell: A Molecular Approach

Inflammatory processes in muscle injury and repair (correct)

What key process is highlighted in Kumar, Abbas, and Aster's textbook?

Inflammation and repair in disease Signup and view all the answers

Which book primarily focuses on skeletal muscle physiology and trauma responses?

Skeletal Muscle Structure, Function, and Plasticity Signup and view all the answers

What is the primary role of phospholipids in cell membranes?

To form a double layer that separates the cell from its environment Signup and view all the answers

What is a consequence of direct trauma to membrane proteins?

Altered functionality and potential cell death Signup and view all the answers

Which of the following best describes the interaction between the cell membrane and cytoskeleton?

The cytoskeleton maintains cellular structure by anchoring the cell membrane Signup and view all the answers

In the context of mitochondrial dynamics, what happens during ischemia and reperfusion?

Release of reactive oxygen species and potential mitochondrial dysfunction Signup and view all the answers

How does the immune system respond to cellular injury?

Through the release of pro-inflammatory cytokines and immune cell recruitment Signup and view all the answers

What is a potential complication of persistent inflammation and ineffective repair?

Fibrosis and heart failure Signup and view all the answers

What is a key pathophysiological mechanism involved in myocardial infarction?

Decreased blood flow leading to tissue ischemia Signup and view all the answers

Which of the following describes the excitation-contraction coupling mechanism in skeletal muscle?

Release of calcium from the sarcoplasmic reticulum triggering muscle contraction Signup and view all the answers

What is the primary composition of the cell membrane?

Phospholipid bilayer with proteins Signup and view all the answers

Which of the following is NOT a function of the cell membrane?

Synthetic protein production Signup and view all the answers

How does the cytoskeleton contribute to the cell membrane?

It provides structural support Signup and view all the answers

What effect can physical trauma have on the cell membrane?

It can disrupt membrane structure Signup and view all the answers

Which downstream effect can result from membrane damage?

Tissue inflammation Signup and view all the answers

Why is membrane integrity critical for cellular homeostasis?

It regulates ion concentrations. Signup and view all the answers

What type of structure is the phospholipid bilayer considered?

Dynamic and fluid Signup and view all the answers

What role do membrane proteins play in the cell membrane?

They assist in signaling and transport. Signup and view all the answers

Which of the following best describes the cell membrane's function in energy production?

It facilitates chemical energy transfer. Signup and view all the answers

What is a consequence of disrupted membrane integrity?

Diminished mitochondrial function Signup and view all the answers

What is a potential complication of prolonged medication use related to liver function?

Hepatotoxicity Signup and view all the answers

What role does IGF/FGF play in muscle regeneration?

Stimulates quiescent satellite cells Signup and view all the answers

What consequence results from excessive TNFα/IL-1β levels in muscular injury?

Formation of fibrotic tissue Signup and view all the answers

What event triggers action potentials in cardiomyocytes?

SA node pacemaker potential Signup and view all the answers

What is a significant outcome following myocardial infarction due to arterial blockage?

Downstream ischemia and membrane damage Signup and view all the answers

What mechanism describes the primary method of cardiac repair post-myocardial infarction?

Hypertrophy of surviving myocytes Signup and view all the answers

What consequence does poorly maintained collagen turnover during myocardial repair have?

Increased likelihood of cardiac rupture Signup and view all the answers

What is the consequence of prolonged elevated intracellular calcium in muscle cells?

Activation of proteases Signup and view all the answers

What is a common result of ischemia-induced remodelling in cardiac tissue?

Arrhythmias due to non-uniform repolarization Signup and view all the answers

What symptom was exhibited by the patient with exertional rhabdomyolysis following their long run?

Tea-coloured urine Signup and view all the answers

What primarily causes localized openings or defects in the plasma membrane following direct trauma?

Disruption of lipid tail packing Signup and view all the answers

Which of the following best describes how direct trauma affects integral proteins in the plasma membrane?

Unseats transmembrane helices from the bilayer Signup and view all the answers

What is a consequence of calcium overload during ischemia?

Sharp rise in intracellular Ca2+ concentration Signup and view all the answers

How do anaphylatoxins C3a and C5a affect vascular permeability?

Stimulate contraction of actin cytoskeleton Signup and view all the answers

What triggers the release of cytochrome c during mitochondrial permeability transition?

Collapse of the inner membrane potential Signup and view all the answers

During muscle tear pathophysiology, what effect does eccentric contraction have on the sarcomere structure?

Z-disks rupture and actin-myosin filaments pull apart Signup and view all the answers

What is the primary role of integrins in focal adhesions?

Connect cytoskeleton to membrane Signup and view all the answers

Which of the following describes the function of choline/phosphate head groups in membrane lipids?

Position lipid tails towards the interior of the membrane Signup and view all the answers

What initiates the apoptotic cascade following loss of mitochondrial integrity?

Exodus of cytochrome c from mitochondria Signup and view all the answers

What is the impact of shear and compression forces on membrane lipid organization?

Disruption of tight lipid tail packing Signup and view all the answers

Study Notes

Cell Membrane Structure and Function

The cell membrane is a dynamic and complex structure, critical for cell life.
It acts as a boundary between the cell's internal and external environments.
Primarily composed of a phospholipid bilayer with embedded proteins.
Controls the passage of substances into and out of the cell.
Maintains cellular homeostasis, signaling, and energy production.
The cell membrane's integrity is vital.

Learning Outcomes

Gain a comprehensive understanding of cell membrane composition and architecture, including the role of phospholipids.
Analyze the effects of physical trauma on the membrane's integrity and permeability.
Understand the interplay between the cell membrane and cytoskeleton during stress.
Learn about membrane protein functions and direct trauma consequences.
Investigate cellular responses to trauma including inflammation and apoptosis.
Understand the structural organization and importance of mitochondria in cellular metabolism.
Analyze clinical cases related to muscle and myocardial injury.
Discuss implications of ischemia and reperfusion on mitochondrial function and reactive oxygen species generation.

Membrane Composition and Structure

The membrane is made of a phospholipid bilayer with hydrophilic heads facing outward and hydrophobic tails inward.
Proteins are embedded in the membrane, having diverse functions including transport, signaling, and cell recognition.
Specialized proteins like glycoproteins and glycolipids function in cell communication and recognition.
Cholesterol contributes to membrane fluidity and stability.

Overview

Introduction to the molecular mechanisms involved in cell membrane disruption.
Detailing the signaling cascade during muscle injury.
Covering skeletal and cardiac muscle injury.
Clinical case presentations highlighting injury mechanisms.

Molecular Mechanisms of Cell Membrane Disruption

Chemical disruption through lipid peroxidation and enzymatic cleavage alters membrane fluidity.
Physical breaches such as nanoruptures and membrane tears disrupt the phospholipid bilayer, causing cytosol leaks.
Pore formation creates gaps in the membrane due to physical trauma.

Effects on Membrane Lipid Organisation

Direct trauma (shear/compression) disrupts lipid tail packing.
Physical forces break non-covalent interactions between neighboring lipid tails.
Lipid separation leads to membrane openings where cytosol leaks and selective permeability is lost.

Effects on Membrane Integral Proteins

Transmembrane domains embedded in the phospholipid bilayer anchor proteins in place.
Hydrophobic interactions maintain protein tertiary structure within the membrane.
Direct impact and shearing forces distort protein conformations, displacing transmembrane helices.
Peripheral domains detach from the membrane, affecting protein function (transport, signaling).

Effects on Membrane-Cytoskeleton Interactions

Focal adhesions contain integrin heterodimers that interact with actin fibers.
Integrin cytoplasmic domains attach to actin via adapter proteins.
Forces parallel to the membrane strain these integrin complexes, leading to cytoskeleton detachment.

Increased Lateral Pressure on Membrane

Actin transmits force across membrane integrins putting strain on the cell membrane.
Lipids are stretched beyond tolerable thinning pressure, causing them to separate and no longer pack tightly.

Detachment of Cytoskeleton from Membrane

Strong perpendicular strain overcomes integrin-actin binding strength.
Detaches entire cytoskeletal scaffold from focal adhesions.
Alteration of lipid fluidity from removed constraints.
Changes in membrane curvature and cellular mechanotransduction.

Mitochondrial Structure and Function

Inner and outer mitochondrial membranes enclose cristae and matrix.
Cristae contain the electron transport chain complexes.
Glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation occur within mitochondria.
Essential for ATP production via oxidative phosphorylation.

Ischemia Halts ATP Production

Loss of blood flow cuts off oxygen (O2), the final electron acceptor.
Inhibits cytochrome c oxidase, halting electron transport.
Stops ATP synthesis via oxidative phosphorylation.

Calcium Overload During Ischemia

Lack of ATP inhibits Na+/K+ and Ca2+ ATPases.
Intracellular and mitochondrial Ca2+ concentrations rise sharply, causing damage.

Reactive Oxygen Species Burst

Reperfusion reintroduces oxygen, leading to xanthine oxidase pathway activation.
Damaged electron carriers in the electron transport chain leak electrons to oxygen, producing superoxide radicals (O2-) and hydrogen peroxide (H2O2).
These reactive oxygen species cause damage to the cell.

Mitochondrial Permeability Transition

High Ca2+ triggers the opening of mitochondrial permeability transition pores.
Collapses the proton gradient and membrane potential.
Facilitates the release of molecules damaging the cell.

Cytochrome C Release

Loss of inner membrane integrity releases cytochrome c.
Triggers caspase cascade, leading to apoptosis.

Activation of Complement System & Increased Vascular Permeability

Cell membrane damage exposes cellular antigens and phospholipids.
Activates complement system.
Anaphylatoxins bind to endothelial cells (C3a and C5a)
Stimulates actin cytoskeleton contraction and junction widening.

Neutrophil Recruitment & Pro-Inflammatory Mediator Release

Chemokines and cytokines induce selectins and integrins.
Resulting in neutrophil tethering, rolling, adhesion, and transmigration.
Neutrophils and macrophages secrete inflammatory mediators (TNFα, IL-1β, IL-6) and reactive oxygen species (ROS) to amplify response.

Skeletal Muscle Structure, Excitation-Contraction Coupling & Muscle Tear Pathophysiology

Striated muscle cells with basal lamina and connective tissue sheath.
Multinucleated fibers formed by myoblast fusion.
Neuromuscular junction depolarization triggers inward calcium current.
Calcium binds troponin C, exposing binding sites on actin for myosin cross-bridges.
Direct blunt force or eccentric contraction leads to sarcomere stretching beyond limits.
Ruptures Z-disks, pulling apart actin-myosin filaments.

Mechanisms of Rhabdomyolysis

Prolonged ischemia exhausts energy stores and Na+/K+ ATPase function.
Sarcoplasmic calcium accumulation triggers proteolysis of contractile proteins.

Clinical Case of Quadriceps Tear

28M presents with acute thigh pain after a rugby tackle.
Unable to fully extend knee, crepitus present.
MRI shows a partial distal quadriceps tendon tear.
A 23-year-old male presents with left thigh pain following a soccer injury.
Examination reveals a swollen thigh and inability to fully extend the knee.
Compartment syndrome is suspected as a likely diagnosis.

Clinical Case of Medication Complication

Female taking medication following a heart attack.
Increased fatigue and swelling of legs observed.
Hepatotoxicity from the medication is a potential complication.

Inflammation and Membrane Repair, Satellite Cell Activation & Regeneration of Myofibers

Damaged membranes activate kinin-kallikrein and complement pathways.
Neutrophils clear debris and release TGFβ/IGF for regeneration.
IGF/FGF stimulates quiescent satellite cells adjacent to basal lamina.
Satellite cells proliferate, fuse, and differentiate into new myofibers.
Myotubes align, fuse nuclei, and reform motor endplates.

Persistent Inflammation Complications & Clinical Case of Exertional Rhabdomyolysis

Excessive TNFα/IL-1β causes fibrosis instead of regeneration.
Transforming growth factor beta promotes collagen deposition.
A 42-year-old female collapsing after a long run, with tea-colored urine, and elevated CK (100,000 U/L).
Demonstrates acute kidney injury.

Membrane Disruption in Ca2+ Toxicity & Proteolytic Degradation of Muscle

High intracellular Ca2+ activates phospholipases and proteases.
Leads to phospholipid hydrolysis and membrane protein denaturation.
Calpains and cathepsins cleave cytoskeletal and contractile proteins.
Triggers oncosis and myoglobin/protein release into the bloodstream.

Cardiomyocyte Structure & Excitation-Contraction Coupling

Branched, striated cardiomyocytes connected via intercalated discs.
Higher mitochondria content for aerobic metabolism.
SA node pacemaker potential activates action potentials.
Voltage gated L-type Ca2+ channels open, allowing calcium to enter the cytoplasm.

Pathophysiology of Myocardial Infarction & Clinical Case of STEMI

Coronary artery plaque rupture causes thrombosis and vessel occlusion.
Ischemia and calcium/ROS mediate membrane damage downstream.
62M presents with crushing chest pain radiating to the left arm.
EKG shows ST elevations in lateral leads, elevated troponin.
Cardiac resynchronisation therapy is the appropriate management strategy.

Physiological Repair After MI, Limitations of Cardiomyocyte Regeneration & Arrhythmias After MI

Inflammation clears necrotic myocytes.
Fibroblasts deposit collagen scar tissue in infarcted areas.
Post-mitotic cardiomyocytes have limited proliferation after early neonatal period.
Repair by surviving cardiomyocyte hypertrophy.
Ischemia-induced connexin remodeling causes non-uniform repolarization.
Substrate for reentry circuits leads to lethal ventricular arrhythmias.

Heart Failure After MI & Molecular Basis of Cardiac Rupture

Loss of contractile tissue leads to compensated dilation and hypertrophy.
Eventually leads to dilated cardiomyopathy if the defect is substantial.
Imbalance in collagen turnover during repair weakens the infarct zone.
Scar tissue might rupture due to inability to withstand wall stress during contraction.

Summary

Cell membrane serves as an interface for cellular integrity and injury.
Traumatic impacts and ischemic repercussions have significant consequences.
Inflammatory response and cell death pathways in muscle injury are outlined.
Clinical cases illustrate muscle injury from molecular insights.
Cardiac muscles have specific responses to injury.
Comparative molecular insights to injury are explored.
Concluding thoughts on the presented material.

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Description

Explore the dynamic structure and essential functions of the cell membrane, including its composition and role in maintaining cellular integrity. This quiz covers topics such as phospholipid bilayers, membrane proteins, and the effects of trauma on cellular functions. Understand the crucial interactions between the cell membrane and its environment.