The Cell as a Unit of Health and Disease

physiology

the study of normal process in your body  

pathology

study of disease processes  

pathophysiology

study of the processes that get disturbed during the disease state 

etiology

cause

pathogenesis

the sequence of events that follows after the exposure of a cell to an injurious agent 

4 components of disease pathology

etiology, pathogenesis, clinical features, morphologic changes

genetic etiology

inherited mutations

disease associated gene variants: will not cause the disease, but will put you at risk for having the disease; ex. BRACA  

acquired etiology

infections, nutritional, chemical, physical

sign

what you observe and measure';objective

symptom

what the pt tells you; subjective  

acute

4 weeks

subacute

4-12 weeks

chronic

>12 weeks

cellular housekeeping

Functions that must happen within the cell no matter what (irrespective of the state of the cell)  

Protection, movement, absorption, communication, catabolism, energy generation, excretion

movement

some cells are always moving (ex. Blood cells)  

communication

ex. Virally infected cells release interferons to tell other cells, or growth factors  

catabolism

break down complex molecules to simple substances  

energy generation

ATP

functions of plasma membrane

• Give protection and nutrient acquisition  

• Acts like a scaffold – binds to receptors, give surface area for binding  

• Signaling mechanism  

• Apoptosis – plasma membrane flips open and eposes a signal for cell death  

plasma membrane structure

Lipid bilayer: hydrophilic outside, hydrophobic inside 

membrane transport

• Active needs ATP; passive doesn’t need ATP  

• Passive down gradient; active against  

types of passive transport

• Diffusion – high to low concentration – needs to be less than 15 angstrom – small in size and less than 100 Daltons in mass, and not charged  

• Osmosis – water 

• Facilitated – channel protein or carrier protein; channel protein opens and closes like a door; carrier protein is like a revolving door  

types of active transport

• Endocytosis: coming in cell  

• Pinocytosis: cell drinking  

• Phagocytosis: ex. Macrophage  

• Exocytosis: going out of the cell – hormones are released through exocytosis  

cytoskeletal protein functions

Shape, structure, mechanical support, polarity to cells  

actin filaments

• <10 nm 

• One of the most abundant proteins in your body 

• Functions: movement within cell, cytokinesis, cell contraction (actin and myosin - muscle contraction) shape, endo and exocytosis  

intermediate filaments

• 10 nm 

• Distribute mechanical stress that the cell experiences  

• Ex. Keratin  

microtubules

• 25 nm  

• Most versatile cytoskeletal protein 

• Transport  

• Ex. Sperm flagella  

• Dynamic protein: cilia, chromosome cell division  

tight junctions/occluding junctions

• certain cells don’t pass anything between them  

• Ex. Bladder  

gap junctions/communicating junctions

• 1.5 – 2 nm pores 

• Ex. Heart cells, some neurons  

anchoring junctions/desmosomes

Act like a glue and are helpful in distributing mechanical stress ex. Skin, intestine

ER function

protein synthesis

rough ER

ribosomes attached which synthesize protein that are destined to go to the plasma membrane  

smooth ER

lipid synthesis, steroid hormone synthesis, glycogen metabolism, storage of calcium  

• Calcium should be within the ER or mitochondria – calcium in cytoplasm —> apoptosis  

chaperones

fold the proteins so hydrophobic inside and hydrophilic outside 

sarcoplasmic reticulum

ER of the muscle

golgi apparatus

USPS of the cell, sends proteins to their location 

lysosomes

contain active hydrolases

• degradation - degrade anything into smaller components/individual components

heterophagy

substance comes from outside ex. Bacteria  

autophagy

• substance comes from inside  

• All cellular organelles have to be recycled when they are defective —> merge into lysosome  

• Limited is a good cleansing mech for your cell, but too much is bad  

proteosomal degradation

• Break down proteins  

• Can recognize protein that needs to be degraded by tagging of ubiquitin  

• Degrades into fragments/chunks that need to be further degraded  

• Proteosomes not functioning —> Alzheimer’s, Parkinson’s  

mitochondria

• Genome considered to be very effective – 37 genes 

• Functions:  

• Oxidative phosphorylation: ATP produced  

• Apoptosis: mitochondria become leaky – cytochrome C in cytoplasm —> apoptosis  

• Anabolism: heme synthesis, beta oxidation of fatty acid, provide precursors for certain AA synthesis  

• Matrilineal inheritance – disease only through females  

ROS

• Byproduct of cellular reactions 

• Limited by antioxidants  

• Signaling processes 

• Excess cause disease – smoking, alcohol, pollution, radiation  

• Oxygen radical with free electron in the outer orbital  

• Superoxide, hydroxide, peroxide 

• Catalase, superoxide dismutase (SOD) = antioxidants  

• Imagine a bullet piercing through a cell – plasma membrane, cytoplasmic protein, DNA damage  

necrosis

• Accidental cell death  

• Always pathological  

• External agents 

• ATP depletion —> cell starts swelling —> burst  

• Messy cell death  

• Inflammation  

• Group of cells die – massacre equivalent  

apoptosis

• Programmed cell death  

• Physiological or pathological  

• External and internal agents  

• Leaky mitochondria  

• Cell shrinks  

• Can happen to single cells – suicide equivalent  

cell signaling and abnormal signaling

• Pathogens, growth factors, external environment  

• Too much signaling —> cancer = uncontrolled growth  

• Too little - suck like in shock – organ dysfunction and failing  

paracrine

nearby – ex. Acetylcholine signaling in muscle cells in nearby area  

autocrine

• self-stimulation – ex. T cells 

• APC brings pathogen to T cell – releases interleukins – can cause clonal proliferation of T cell  

endocrine

• hormones released in blood and act at distant targets  

• Always need ligand and receptor for signaling  

intracellular receptor

Ex. Nuclear receptors for vitamin D  

cell surface receptor

ex. GPCR , Receptor tyrosine kinases – phosphorylate tyrosine residues  

ECM

external environment the cell has; a network of interstitial proteins that constitutes a significant proportion of any tissue  

Cell interactions with ___ are critical for development and healing, as well as maintaining normal tissue architecture  

ECM functions

mechanical support, control of cell proliferation, tissue microenvironments (ex. Basement membrane of kidney)  

interstitial matrix

• Type 1 collagen, proteoglycan, hyaluronan  

• Filler between cells  

basement membrane

• type IV collagen, proteoglycan 

• Helps create boundary; separate layers – epithelial cells from connective tissue  

interstitial matrix location

Present in spaces between connective tissue, and between parenchymal epithelium and underlying supportive vascular and smooth muscle structures  

basement membrane location

the ECM that surrounds epithelial cells, endothelial cells, and smooth muscle cells and separates them from connective tissue  

cell proliferation

how fast cells divide

• highly proliferating cells will delay differentiation

cell differentiation

how fast cells mature

• poorly differentiated = more aggressive cancer

cell processes contributing to maintain balance

• Proliferation, differentiation, regeneration, death rate  

cell cycle phases

• G0: highly differentiated cell in G0 

• G1: the cell becomes bigger – synthesize materials for division  

• S: DNA replication  

• G2: pre-mitotic; DNA error check; if error use DNA repair system; if unable to repair, cell cycle arrest  

stem cells

differentiate and form multiple cell types

stem cell properties

1. Self-renewal: unlimited cell division without senescence  

2. Clonogenic:  1 cell can make its own clone 

3. Multipotent: form more than 1 cell type 

4. Asymmetric division: 1 daughter cell, 1 stem cell  

symmetric vs asymmetric division

• Symmetric division: 1 mother cell --> 2 daughter cells 

• Asymmetric division: 1 mother stem cell --> 1 mature cell, 1 daughter stem cell

totipotent

can form anything, including placental tissues  

pluripotent

anything but placental tissues  

multipotent

multiple cell types of the same lineage  

oligopotent

form 2-3 cell types  

unipotent

1 cell type  

embryonic stem cell

• Zygote is totipotent and early blastomeres are totipotent  

• Day 3-4: morula – totipotent  

• Day 4-5: develops into a blastocyst – pluripotent  

• Embryonic stem cells from inner layer of the blastocyst are pluripotent  

tissue stem cells

• Adult stem cells  

• Multi- to oligopotent  

• Stem cells are sleepy and are woken up ex. Wake up liver with chronic alcohol exposure  

simple squamous epithelium

1. Function: passage of material by diffusion and filtration  

2. Location: kidney glomeruli, alveoli, capillaries  

stratified squamous epithelium

1. Function: protection  

2. Location: skin, lining of mouth and esophagus 

simple cuboidal epithelium

1. Function: secretion and absorption 

2. Location: kidney tubules, ducts of glands, ovarian surface  

simple columnar epithelium

1. Function: absorption, secretion of mucus and enzymes  

2. Location: digestive tract, gallbladder  

transitional epithelium

1. Function: stretching  

2. Location: urinary bladder  

skeletal muscle

Function: voluntary movement  

cardiac tissue

• Function: involuntary contraction to propel blood  

• Location: heart  

smooth muscle

• Function: involuntary, propels substances  

• Location: walls of hollow organs  

nervous tissue

• Function: transmit signals  

• Location: nerves, brain, spinal cord 

bone

Function: support and protect  

hyaline cartilage

1. Function: supports, reinforces, cushions 

2. Location: ribs, nose, embryo 

fibrocartilage

1. Function: absorb shock  

2. Location: discs  

elastic cartilage

1. Function: maintains shape  

2. Location: ear  

dense tissue

1. Function: attaches bone to bone or muscle to bone  

2. Location: tendons and ligaments 

adipose tissue

1. Function: cushioning, heat source, energy source  

2. Location: under skin  

reticular tissue

1. Function: fibers support other cells 

2. Location: spleen, bone marrow, nodes  

blood

1. Function: transport nutrients  

2. Location: arteries and veins