Cell Biology

Review and Altered Functions

Embryonic Stem Cells

Man Made Stem Cells

Adult Stem Cells

Major Parts

Eukaryotic Cell Structure

Cell Functions

CommunicateAbsorbSecreteExcreteRespireMoveConductReproduce

What is the “Brain” of the cell?

Cell Membrane (“membrain”)

StructureFunctionReceptorsJunctionsSignal TransductionTransport Gradients

ConcentrationDependentIndependent

Electrical Pressure

Bulk Transport

Cell Membrane Proteins

Na+/K+ Pump

Cell Junctions

Adhesion Molecules

Cell Adhesion Molecules (CAM)Bind growth factors

CadherinsBind cell membranes to form junctions

SelectinsBind WBCs during inflammatory reactions

IntegrinsBinds extra cellular matrix proteins

Cell Junctions

Cancer Metastasis

Cell Signals

Hormone vs. Neurotransmitter

Target Cell

Receptors

Cell Receptor Summary

Abnormal Intercellular Communication

Alterations in Membrane:

enzymes, ionsreactive oxygen species

(ROS) Adhesion molecules:

defense, clotting, metastasis

Gradients: water, ions, glucose

Transport Proteins: pumps, channels

Signaling molecules: hyper/hypo production

Receptors: destroyed, blocked,

triggered

Mitochondria

Cellular Metabolism

MacromoleculesEnergy Requirements:

BMR, TMR

Energy FormsMetabolic Pathways

Glycolysis Aerobic Respiration Beta Oxidation Deamination

Metabolic Pathways: Aerobic

Krebs Cycle

Metabolic Pathways: Proteins & Lipids

Metabolism Summary

Metabolic Alterations Alterations

Impaired Input MalnutritionMalabsorption

Impaired BalanceHypoxiaToxicityTraumaGenetic

Demand ChangesHypometabolic State

• Aging,• Immobility

Hypermetabolic State• Pregnancy• Hypothermia• Wound healing• Stress

Alcohol Metabolism

Cell Cycle

Cell Divisions Compared

Tissue Types

Tissues

RepairRegenerationScar Tissue

DeathApoptosisNecrosis

Mechanisms of Cellular Injury

Response depends on Type of injury Duration Severity

Consequences depend on Type of cell Current physiology of cell Adaptability

Vulnerable cell sites Cell Membrane Mitochondria Nucleus

Hypoxia Ischemia Oxidants

Causes of Cellular Injury

PhysicalChemicalMicrobialImmunologicGeneticNutritionalAging

Toxic, Chemical, or Physical Injury

ChemicalEnvironmental agentsDrugsMetabolites

PhysicalTraumaTemperatureRadiation

Heat Injury to RBCs

Pathogenesis example

Sequella to injury

Changes due to injury

Reversible Injury Processes

Transient if stress is removed Compensatory responses

Full capacity to repair Adaptation with diminished

capacity Cell Responses

Cell swelling (hypertrophy)Na+/K+ pump damagedOsmosis

Fatty changesCell metabolism changesSevere injurySlower to recover

Reversible Injury in the LiverGross Findings

GreasyPaleEnlarged

Cellular Metabolism StopsDisruption of Beta

OxidationFA TriglyceridesCytoplasmic fat

droplets

Fatty Liver

Hypoxia and Ischemia

Define HypoxiaEnd results

ATP production changes

Anaerobic mechanismspH changes

Organ DiseasesLungsHeartBlood VesselsBlood

Define IschemiaEnd results

Hypoxia Infarct

Organ problemsArteriesVeins

Ischemia Infarct Necrosis

Coagulative necrosis in the kidney

Ischemia Pathway

Reversible Injury from Hypoxia/Ischemia

Decreased Oxidative phosphorylation

Decreased ATPDepletion of glycogenDecreased pHDecreased protein

synthesisElectrolyte changes

Na+ K+ Ca++

Increased osmosisSwollen organelles

Small Intestine

Stress and Intracellular Changes

CytoskeletonLysosomesMitochondriaSERIntracellular

accumulationsFatProteinGlycogenPigmentsCholesterol

Stressors and Cell Death

Lipofuscin Pigment in hepatocytes

Irreversible Injury from Hypoxia/Ischemia

Cell Membrane injury Free radical formationLipid breakdownLysosomal enzyme

release Ribosomes Nuclear changes Protein digestion

Ca++ accumulates in mitochondria

Activation of Inflammatory chemicals

Lung

Pathological Calcification

Dystrophic CalcificationOccurs in dead, dying, or damaged tissue

AtherosclerosisHeart Valves

Metastatic CalcificationOccurs in hypercalcemic states

Renal FailureSecondary Hyperparathyroidism

Free Radical Formation and Damage

Effects of Oxidative Stress

Enzymes involved in Oxidative Stress

Mitochondrial Function and Damage

Mitochondrial Damage

Release of Cytochrome C

Mitochondrial Changes in Injury

DNA damage

Antioxidants

Reversible vs Irreversible DamageCardiac Function

Cellular Adaptations

PhysiologicUp or down regulationProtein synthesisAtrophyHypertrophyHyperplasia

Pathological AtrophyHypertrophyHyperplasia /

DysplasiaMetaplasia

Atrophy

Hypertrophy

Hypertrophic Cardiomyopathy

Hyperplasia

Metaplasia and Dysplasia

Necrosis Morphological Types

Coagulative Necrosis Protein coagulation due to acidosis MI

Liquefactive Necrosis Complete digestion of dead cells Nervous system, Bacterial and Fungal Diseases

Gangrenous Necrosis Ischemic coagulative necrosis Post op

Caseous Necrosis Amorphous granular debris (cheese like appearance) TB infections

Fat Necrosis Fat destruction due to liquefaction Fatty acids combine with calcium to create chalky white areas (saponification) Pancreatitis

Liquefactive Necrosis in the brain

Necrosis

Caseous Necrosis (lung)

Gangrenous Necrosis

Skin

Apoptosis

Differences between cell death:Necrosis and Apoptosis

Necrosis Contiguous cells Membrane loss Gradient changes Organelles swell Nucleus

Pyknosis (shrinks)Karyorrhexis (fragment)

Apoptosis Individual cells Normal process Cells shrink Fragmented bodies Phagocytosis

Factors in Cell Death

Necrosis stimulates inflammation

Tissue Repair

Tissue TypesParenchymal (fxn)Stromal (CT)

RepairRegenerateReplacement

Regenerating AbilityLabile cells Stable cells Permanent cells

Tissue Repair and Chronic injury

Cellular Aging Theories

Cellular SenescenceLoss of redundant DNA sequencesRadom errors/mutations/repair Free Radical DamageTelomere ShorteningDecreased heat shock responseGlycosylation of proteins and NAMetabolic Rate (inverse)Homeostatic Systems decline

Cellular Damage vs Repair Cycle

Summary of Cellular Damage Events

Examples of someDiseases/ConditionsCaused by alterations In Cell Function

Questions?