Patho 1

Overview: From organelles to organ systems

• We start at the smallest functional unit (organelle inside the cell) and build up to the organism

• Organelles are cell “body parts”; cells group into tissues; tissues form organs; organs form organ systems

• Focus of the course: dysfunction and how small problems at the cellular level can have systemic, real-world effects

• Emphasis on somatic cells (non-sex cells) such as red blood cells, muscle cells, osteocytes, neurons; sex cells (sperm/egg) are not the focus

• The nervous system and muscles are important but will be addressed in later lectures

• The body is likened to a well-tuned engine; disease often arises when one part misfires or malfunctions

• Real-world relevance: many people have experienced illness, inflammation, or tissue injury; these examples help relate to cellular processes

The basic cell organization: organelle → cell → tissue → organ → organ system

• Organelle: a functional component inside a cell (e.g., nucleus, mitochondria, lysosomes)

• Cell: basic structural and functional unit of life

• Tissue: group of similar cells performing the same function

• Organ: group of tissues working together

• Organ system: multiple organs functioning cohesively

• Humans are highly integrated systems of organ systems

Core cell structures: plasma membrane, cytosol, organelles

• Plasma membrane = outer boundary of the cell; phospholipid bilayer

• Lipid bilayer organization:

  • Hydrophilic (water-loving) polar heads on outside/inside surfaces

  • Hydrophobic (water-fearing) fatty acid tails face inward

  • Fluid mosaic with embedded proteins

• Cytosol: intracellular fluid inside the cell but outside organelles

• Organelles inside the cell include nuclei, mitochondria, Golgi, endoplasmic reticulum, lysosomes, peroxisomes, centrioles, cytoskeleton, etc.

• Important note: to understand tests, study everything discussed in readings and lectures unless directed otherwise by the instructor

Nucleus and genetic control

• Nucleus: the brains/center of the cell; contains genetic material directing cell activities

• Nuclear envelope: a double-layered, porous membrane that regulates entry/exit of signals

• Inside the nucleus: chromosomes containing DNA; DNA is the genetic material

• RNA present in the nucleolus (component of messenger and transfer ribosomal RNA)

• Nucleolus: spherical structure within the nucleus; primary site for ribosome production and assembly

• DNA and RNA processes (transcription/translation) are noted but not covered in depth here due to course scope

The nucleolus and ribosomes

• Nucleolus: site of ribosome production and assembly

• Ribosomes: carry out protein synthesis

• End result: genetic information is used to produce functional proteins that drive cellular function

Lysosomes, peroxisomes, and cellular digestion

• Lysosomes: digestive organelles containing enzymes that break down waste materials and damaged components

• Function: digestion within phagocytic processes; integral to apoptosis (controlled cell death)

• Peroxisomes: contain enzymes that decompose hydrogen peroxide (H₂O₂) and other toxins

• Lysosomes/phagolysosome activity is essential for cellular maintenance and turnover

Mitochondria: powerhouses with their own DNA

• Function: convert food/materials into usable energy (ATP)

• ATP (adenosine triphosphate) = energy currency of the cell

• Mitochondria contain their own DNA (endosymbiotic origin) and can produce ATP independently

• ATP structure (conceptual): ext{ATP}
  ightarrow ext{ADP} + ext{P}_i + ext{energy}

• ATP hydrolysis and energy release drive cellular processes; phosphate groups are cleaved to release energy

• ATP can be regenerated from ADP and inorganic phosphate: ext{ADP} + ext{P}_i
  ightarrow ext{ATP}

• Mitochondria communicate with other organelles via the endoplasmic reticulum for coordinated function

Endoplasmic reticulum (ER) and Golgi apparatus

• Endoplasmic Reticulum (ER): network of membranous tubules that communicates with the nucleus and other membranes

  • Rough ER: studded with ribosomes; site of protein synthesis destined for secretion or membranes

  • Smooth ER: lacks ribosomes; involved in lipid synthesis

• Golgi apparatus: “FedEx/UPS of the cell”; modifies, sorts, and packages proteins and lipids for transport

• Synthesis of large carbohydrate molecules occurs in the Golgi

• Proteins from rough ER move to Golgi, join with carbohydrates to form secretory granules for export or other functions

The cytoskeleton and cell structure

• Cytoskeleton: network of protein filaments that provide structural support, shape, and intracellular transport

• Three main types of filaments (from largest to smallest):

  • Microtubules (largest)

  • Intermediate filaments

  • Microfilaments (smallest)

• Function: reinforces cell interior, maintains cell shape, positions organelles, aids in movement

• Diagnostic/prognostic potential: certain intermediate filaments can indicate disease type or prognosis (e.g., tau protein changes in Alzheimer's disease affecting microtubule stability)

• Actin (a major component of microfilaments) participates in movement and structural dynamics; cytoskeleton supports cellular function and protein synthesis pathways

The plasma membrane and transport across it

• Phospholipid bilayer with hydrophilic heads and hydrophobic tails creates a selective barrier

• Integral (intrinsic) proteins create pores/channels or transport pathways across the membrane

• Transport mechanisms across the membrane:

  • Passive transport (no energy required): diffusion, facilitated diffusion via channels or carrier proteins

  • Diffusion: solutes move down their concentration gradient (high to low)

  • Facilitated diffusion: via channel proteins (tunnels) or carrier proteins (one molecule at a time)

  • Active transport (requires energy, usually ATP): moves substances against their concentration gradient (low to high)

• Examples/analogy ideas: moving molecules into/out of the cell to maintain homeostasis

• Osmosis: movement of water across a selectively permeable membrane; balance of solute concentrations across compartments

• Homeostasis and isotonic balance: the cell’s goal is to maintain proper volume and composition; hypotonic/hypertonic conditions can cause swelling or shrinkage

• Exocytosis: active process to eject material from the cell; requires energy (e.g., secretion of waste or signaling molecules)

• Endocytosis: cellular uptake; two main forms discussed

  • Phagocytosis: engulfment of solid particles; forms a phagosome/food vacuole; important in immune response and debris removal

  • Pinocytosis: uptake of liquids in small vesicles; less energy-intensive than phagocytosis

• Endo/exocytosis require energy for vesicle formation and transport

Endocytosis specifics and vesicle trafficking

• Phagocytosis: engulfment of large particles; debris or pathogens; forms a vacuole for digestion

• Pinocytosis: uptake of extracellular fluid and dissolved solutes via small vesicles

• Implications for immunity: some phagocytosis is part of the immune response to pathogens and debris

From cells to tissues: pathophysiology basics

• Hyperplasia: increase in the number of cells in a tissue or organ; controlled cell division in response to increased demand or stimulation

  • Example: hormonal hyperplasia in breast tissue during pregnancy to support lactation

  • Compensatory hyperplasia: liver regeneration after partial hepatectomy; liver can regenerate to a functional extent

• Hypertrophy: increase in the size of individual cells (not number)

  • Example: muscle hypertrophy from exercise; cardiac hypertrophy due to high blood pressure (unwanted in the heart)

• Metaplasia: reversible change in one adult cell type to another type due to chronic irritation/inflammation (e.g., squamous metaplasia in smokers’ respiratory epithelium)

  • Risk: may increase susceptibility to further damage or malignancy if irritant persists

• Dysplasia: abnormal growth/development of cells within a tissue; variation in cell size/shape; often considered precancerous (not cancer itself)

  • May lead to biopsy/histology to monitor progression toward cancer

• Necrosis: uncontrolled cell death due to irreversible damage (toxins, infection, ischemia); characterized by cell swelling, organelle dysfunction, inflammation; can trigger broader tissue damage

• Apoptosis: programmed cell death; controlled dismantling of a cell with little/no inflammatory response; essential for development, homeostasis, immune function

• Aging: cellular aging leads to gradual decline in cellular reliability and function; influenced by environment, toxins, and genetics; lifestyle can impact the aging process

Mitochondrial diseases and other organelle-specific disorders

• Mitochondrial diseases: defects in mitochondrial function lead to energy deficits

  • Example: Leber’s hereditary optic neuropathy (LHON)

  • Affects retinal ganglion cells; sudden vision loss in young adults; more common in biological males due to maternal inheritance and X-chromosome considerations

  • Mitochondrial DNA mutations impair ATP production in affected cells

  • General point: defective mitochondria can cause severe energy shortages in specific tissues

• Endoplasmic reticulum disease example: Cystic fibrosis (CF)

  • Mutation in CFTR gene affects chloride ion transport; CFTR misfolding leads to ER OST block and accumulation of misfolded protein

  • Consequences: thick mucus in lungs and digestive tract; chronic infections and digestive issues; prognosis has improved with therapies, but CF remains severe

• Lysosomal storage diseases example: Gaucher’s disease

  • Deficiency of enzyme glucocerebrosidase; accumulation of undigested materials in lysosomes

  • Clinical consequences: enlarged spleen/liver, anemia, bone pain; nervous system involvement leads to severe outcomes

Tissues: major classes and chief features

• Four major tissue classes:

  • Epithelium: lines surfaces and cavities; forms glands; avascular (no blood vessels) and nourished by diffusion; includes parenchymal (functional) cells; lines exterior and internal surfaces

  • Connective and supporting tissue: most abundant; provides structure and support; includes fibrous, elastic, and reticular fibers; examples include dense connective tissue, adipose tissue, areolar tissue, bone, and blood (blood is a connective tissue because it contains cells in a matrix)

  • Muscle tissue: three types—cardiac, skeletal, smooth; generate force and enable movement

  • Nervous tissue: transmit electrical signals; composed of neurons and glia (supporting cells)

• Epithelium types (structural varieties):

  • Simple squamous: single cell layer; diffusion/filtration; found in air sacs of lungs, lining of heart/blood vessels; delicate and reparative when damaged

  • Simple cuboidal: secretion and absorption; found in secretory portions of small glands and kidney tubules

  • Simple columnar: absorption; may secrete mucus/enzymes; found in digestive tract; may contain cilia in some regions

  • Pseudostratified columnar: secretory and ciliated; typically lines upper respiratory tract (trachea) and helps move mucus

  • Stratified squamous: protective against abrasion; lines mouth, esophagus, and other surfaces

  • Stratified cuboidal: protects and secretes; found in some glands (sweat, salivary, mammary)

  • Stratified columnar: secretes and protects; found in some gland ducts and male urethra

  • Transitional epithelium: allows urinary organs to expand and stretch (bladder, ureters, part of urethra); accommodates urine volume changes

• Connective tissue fibers and components:

  • Collagen fibers: strong and flexible (most abundant protein); provide tensile strength; found in tendons/ligaments; do not stretch much

  • Elastic fibers: provide distensibility; essential for arteries to accommodate blood pressure changes

  • Reticular fibers: form supporting network in soft organs (spleen, lymph nodes, kidneys); form the stroma of organs

• Bone, adipose, areolar, and other connective tissues provide structural support and nutrient delivery for tissues and organs

• Blood as connective tissue: plasma matrix with suspended cells (white/red blood cells); plasma is the liquid matrix with blood cells embedded

Muscle and nerve tissues

• Muscle tissue: three types with distinct features

  • Cardiac muscle: striated, branched, usually uninucleated; involuntary; forms the heart walls (myocardium); electrical conduction roles are important for heart rhythm

  • Skeletal muscle: striated, tubular, multinucleated; voluntary control; responsible for body movement

  • Smooth muscle: non-striated, spindle-shaped, uninucleated; involuntary; lines internal organs (e.g., intestines) and vessels

• Nervous tissue: neurons transmit nerve impulses; glial cells (neuroglia) support neurons

  • Astrocytes: star-shaped, support neurons; important for development and signaling in brain regions (e.g., cerebellum; gait and motion control)

  • Oligodendrocytes (oligodendroglia): form myelin sheath around CNS neurons, enhancing signal transmission

  • Schwann cells: myelinate peripheral nerves; support neuronal survival

  • Microglia: resident innate immune cells of the CNS; phagocytic and debris-clearing

  • Satellite cells: surround neurons in ganglia; roles similar to astrocytes in other regions (supportive functions)

• Myelin basics: Schwann cells and oligodendrocytes create myelin sheaths that insulate axons and speed up signaling

Inflammation: a rapid, coordinated tissue response

• Inflammation is a complex, essential response to injury or infection; it can be local and systemic

• Hallmarks of inflammation include pain, warmth, swelling, redness; these result from vascular and cellular changes

• Key cellular players in acute inflammation:

  • PMNs (polymorphonuclear leukocytes, i.e., neutrophils): first responders; highly phagocytic; exit blood vessels to reach injury site

  • Monocytes/macrophages: arrive later; help clear debris and coordinate resolution

• Vascular changes during inflammation:

  • Capillary dilation: increased diameter and blood flow; causes warmth and redness

  • Increased vascular permeability: leakage of plasma proteins and leukocytes into tissue; leads to edema

  • Leukocyte recruitment and adhesion to endothelium: leukocytes migrate to the injury site

• Systemic inflammatory responses:

  • Fever and systemic cytokine release; leukocyte activation and cytokine signaling can become systemic

  • Cytokines and chemokines: chemical messengers that amplify the inflammatory response; can serve as biomarkers in diagnostics

• Key mediators and molecules involved:

  • Histamine and serotonin: from mast cells; histamine is a vasodilator increasing vascular permeability

  • Prostaglandins (lipids) and leukotrienes (lipid mediators): derived from arachidonic acid; coordinate inflammation

  • Bradykinin: vasodilator; increases vascular permeability

  • Arachidonic acid: a membrane phospholipid precursor to prostaglandins and leukotrienes

  • Complement system: cascade of 9 proteins activated by antigen–antibody reactions; further details to be covered next week

• Chemical mediators can be produced by various cells and plasma; they regulate inflammation; excessive mediators can cause tissue injury

• Lysosomal enzymes released by neutrophils/monocytes can contribute to tissue injury if unregulated

• Anti-inflammatory therapies (e.g., adrenocorticosteroids) can suppress inflammation by affecting the hypothalamic-pituitary-adrenal axis; long-term use risks adrenal suppression

• Inflammation progression model: initiation → amplification → resolution

  • Pattern recognition receptors (PRRs) recognize PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns)

  • Dysregulation of PRRs can cause excessive inflammation and tissue damage

  • Activated immune cells (macrophages, dendritic cells, mast cells) release cytokines/chemokines; if cytokine release is uncontrolled, a cytokine storm can occur, potentially causing systemic inflammatory response syndrome (SIRS) and organ dysfunction

  • Proper resolution involves anti-inflammatory signals and phagocytosis of debris; failure to resolve can lead to chronic inflammation and diseases (e.g., arthritis, inflammatory bowel disease, COPD)

  • Chronic inflammation can lead to fibrosis and organ dysfunction; severe cases may require transplantation

• Relevance to clinical scenarios:

  • Acute injuries typically resolve with minimal intervention

  • Severe or dysregulated inflammation may require medical management to prevent permanent damage

Disease-focused examples tied to organelles and tissues

• Mitochondrial diseases (energy deficiencies): Leber’s hereditary optic neuropathy (LHON)

  • Affects retinal ganglion cells; sudden vision loss in young adults; more common in biological males due to maternal inheritance patterns

  • Mitochondrial DNA mutations lead to impaired ATP production in affected cells

• Cystic fibrosis (ER-associated): CFTR gene mutation affects chloride transport; mucus buildup in lungs and digestive tract

  • Defective CFTR protein leads to misfolding and accumulation in the ER; disrupted ion transport causes thick mucus and chronic infections

• Gaucher’s disease (lysosomal storage): deficiency of glucocerebrosidase; buildup in lysosomes leads to spleen/liver enlargement, anemia, bone pain; nervous system involvement is particularly severe

Key exam-oriented takeaways

• Know the hierarchy: organelle → cell → tissue → organ → organ system

• Distinguish somatic cells from germ cells; understand which cell types are emphasized in this course

• Be able to describe the major organelles and their core functions: nucleus, nucleolus, ribosomes, ER (rough vs smooth), Golgi, mitochondria, lysosomes, peroxisomes, centrioles, cytoskeleton

• Understand membrane structure and transport: phospholipid bilayer, hydrophilic/hydrophobic regions, integral proteins, diffusion, facilitated diffusion, active transport, osmosis, homeostasis

• Differentiate endocytosis types (phagocytosis vs pinocytosis) and exocytosis; recognize when energy is required

• Recall four tissue classes and their basic features; epithelial subtypes and their typical locations/functions

• Recall connective tissue fibers and their roles (collagen, elastin, reticular fibers) and examples of connective tissues

• Understand muscle tissue types and nervous tissue roles; basic glial cell function in the CNS and PNS

• Grasp the basics of inflammation: its stages (initiation, amplification, resolution), hallmarks, and key mediators (histamine, prostaglandins, leukotrienes, bradykinin, cytokines); recognize the concept of cytokine storms and SIRS

• Be able to describe common tissue/disease examples and how they relate to organelles or tissue biology (e.g., LHON, CFTR in CF, Gaucher’s disease, Ehlers-Danlos, osteoarthritis)

• Appreciate the link between cellular dysfunction and systemic disease; how aging and genetics influence cellular processes

Quick reference: essential formulas and numeric references

• ATP hydrolysis (energy release): ext{ATP} + ext{H}2 ext{O} ightarrow ext{ADP} + ext{P}i + ext{energy}

• ATP regeneration: ext{ADP} + ext{P}_i
  ightarrow ext{ATP}

• There are 9 proteins in the complement system (to be explored in more detail next week)

Next steps and review plan

• Review readings to reinforce the organelle functions and tissue types

• Prepare for next week’s focus on immunity, hypersensitivity, allergy, autoimmune disease, and neoplastic disease

• Bring questions to class or email the instructor if anything remains unclear