Histology

bright-field microscope

light microscope

one we use

has obj lens and eye piece

electron microscope

has higher mag than bright field

Transmission EM (TEM)

• shows internal structures

• 2d detailed

Scanning EM (SEM)

• scans topography 

  • 3d surface of structures 

what kind of microscope is this image from

TEM

what kind of microscope is this image from

SEM

Atomic force microscope

similar to SEM but mobile

tip runs over structures, laser reflects light

Body Fluid compartments 

Extracellular fluid 33%TBW

• plasma 20%

• interstitial fluid 80%

intracellular fluid 66% TBW

• intracellular fluid 

how to find total body water 

0.6x body weight 

Plasma membrane

function

• protective barrier

• regulation of transport in and out of cell

  • selectively permeable

features

• amphipathic phospholipid bilayer 

• cholesterol 

  • provides strength and rigidity →allows PM to be more fluid and not fall apart 

• integral proteins 

• peripheral proteins 

• glycoproteins

• glycolipids

integral proteins

embedded in membrane

amphipathic 

functions: 

• channels/pumps/carriers 

• receptors 

• linker / anchor 

• enzymes 

• structural proteins 

  • link neighboring cells 

peripheral proteins

only interact w heads

only on one side of membrane

glycoproteins + glycolipids

glycoproteins

• oligosaccharides attached to integral proteins on extracellular surface

glycolipids

• oligosaccharides attached to heads of membranes 

function:

• cell-cell identification 

• cell-cell signaling 

• attachments for intracellular interactions

Cytoplasm

fluid compartment of cell between nucleus and PM

contains membrane+ non-mem bound organelles + inclusions within cytoplasmic matrix 

Cytoplasmic matrix: 

• water 

• inorganic ions 

• organic molecules

non-membranous organelles

• cytoskeleton

• centrosome 

• ribosome

membranous organelles 

• nucleus 

• Endoplasmic Reticulum 

• golgi apparatus 

• lysosomes 

• peroxisome 

• mitochondria 

cytoskeleton 

complex network of protein subunits that form internal framework of cell 

helps w framework of cell and movement 

3 types : 

• microtubules 

• microfilaments (actin filaments)

• intermediate filaments 

microtubules

features

• non-branching, rigid, hollow tubes of proteins 

• rapidly assemble/dissasemble 

• originates in MTOC 

main protein subunits 

• alpha -tubulin 

• beta-tubulin 

  • uses GTP + Mg2+ to make dimer 

  • dimers stack on top of each other to make tube 

function 

• railway system for intracellular transport 

• maintain cell shape by resisting compression 

• move cells 

• move chromosomes during cell division 

• move organelles

examples 

• motile cilia/flagella

  • 9 doublets + central pair

• non-motile cilia 

  • 9 doublets 

• centriole 

  • 9 triplets 

• spindle fibers

  • cell division 

what is this and what is it made of

motile cilia / flagella

microtubules

• 9doublets and 1 central pair 

what is this and what is it made of 

non-motile cilia 

microtubules 

• 9 doublets

what is this and what is it made of

centriole

microtubules

• 9 triplets

Actin filaments (microfilaments)

features:

• thin, short, flexible protein structures

• in all cell types 

• rapidly assemble and disassemble 

main protein subunits 

• G-actin (globular) proteins 

  • spherical 

  • free actin proteins in cell

• F-actin (filamentous) proteins

  • actin protein polymerized into filaments 

• multiple G-actin come together to make dimer→trimer → multiple F-actin → actin filaments 

  • require ATP + K+ + Mg2+

function 

• maintain cell shape by resisting tension 

• move cells 

• cell division 

• move organelles / cytoplasm 

what is this made of 

Actin filaments 

Intermediate filaments

features

• tough insoluble, rope-like protein structures 

• fixed assembly 

• 2 helical monomers coil → coiled-coil dimer → 2 coiled coil dimers twist → staggered tetramer

main protein subunits 

• class 1+2 = keratins 

  • epithelial cells 

  • mechanical strength 

• class 3= vimentin 

• class 4= neurofilaments 

• class 5= lamins 

• class 6= beaded filaments

functions

• maintain cell shape by resisting tension 

• anchor nucleus and other organelles

what makes up the blue part 

actin/microfilaments

what is this made of

intermediate filaments

what are the gold structures made of

microtubules

what are the red and green parts made of

green - microtubules

red - actin filaments

what is this made of

intermediate filaments

centrosome

made of

• 2 centrioles arranged at right angles

• surrounded by pericentriolar material (PCM)

function 

• Microtubule organizing center 

• stabilize chromosomes during mitosis 

what are these

a centrosome made of 2 centrioles

Ribosomes

features

• 2 subunits made from rRNA

  • 60S= large subunit 

  • 40S= small subunit 

  • 80S= whole ribo

• bound to enzymes

• rRNA strands fold → subunits in nucleolus 

• located unbound in cytoplasm or bound to Rough ER

function 

• protein synthesis via translation of mRNA → amino acid sequences → proteins 

what does S stand for in 60S

Svedburg unit - measures sedimentation rate

Endoplasmic Reticulum

membrane bound network of cisterns continuous w outer envelope of nuclear envelope 

rough ER (granular) 

• has ribos 

• protein synthesis 

  • new proteins fold in lumen of rER → package into vesicles → golgi 

Smooth ER (agranular) 

• no ribos 

• detoxify toxins of GI tract 

• stores intracellular Ca2+

• make lipids, phospholipids, steroids 

where is this from

smooth ER

where is this from

Rough ER

golgi apparatus

network of membrane enclosed discs

2 main networks

• cis golgi network (CGN)

  • toward ER

• trans golgi network (TGN)

  • toward cell membrane 

functions

• post-translational modification of new proteins delivered from rER

  • proteins get modified to increase variability of function

• package and delivery of proteins

types of transport from ER→ golgi 

Anterograde Transport 

• new proteins from rER → CGN

• COP II surrounds transport vesicles

Retrograde Transport

• proteins transported from CGN → rER to be recycled

• COP I 

Destinations for modified proteins from TGN

1. secreted out of cell 

   1. clathrin coated secretory vesicles fuse w PM → exocytosis 

2. integral / peripheral proteins 

   1. non-clathrin coated vesicles fuse w PM 

3. lysosomal enzymes 

   1. clathrin-coated vesicles containing mannose-6-phosphate receptors fuse w lysosomes that have mannose-6-phosphate on them 

what is this 

golgi apparatus 

lysosomes

features

• small-large 

• contains digestive enzymes 

• pH of lysosome = acidic (4.5-5) 

functions 

• digest external structures 

  • fusion w phagosomes → form phagolysosomes 

• autophagy 

  • digest old or damaged organelles through direct fusion w organelles 

• apoptosis

  • programmed cell death

  • immune system tells lysosome if cell is beyond repair → enzymes in lysosome break down rest of cell

Peroxisome

features

• looks sim to lysosome

• contains enzymes for specialized metabolic activities 

functions 

• alpha+beta oxidation

  • break down of long chain fatty acids → shorter fatty acids → eventual ATP prod

• production of plasmlogen

• detoxification

  • converts reactive oxygen species to hydrogen peroxide to o2 and water

  • ethanol metabolism

    • ethanol → acetaldehyde (toxic)→ acetic acid → acetyl CoA → water +CO2

Mitochondria

features

• double membrane

  • outer-smooth

  • inner- folded into cristae+ surrounds matrix 

• intermembrane space 

  • space between 2 membranes 

• intermatrix space 

  • inside space 

• in all cells except RBC

functions

• synthesis of ATP thru aerobic cellular respiration

Nucleus

contains genetic material

DNA

• DNA strands wrap around histones

• tightly coiled → chromatin

  • heterochromatin

    • highly condensed chromatin

  • euchromatin

    • loosely packed chromatin

protected by nuclear envelope

• double membrane separated by perinuclear (cisternal) space

• nuclear pores

nucleolus

• non-membranous

• surrounds transciptionally active DNA → codes for rRNA

• function

  • primary site for ribo production and assembly

Functions of membrane transport 

• obtain nutrients 

• excrete waste 

• maintain electrochemical gradient 

• regulate osmolality +tonicity 

types of membrane transport

• passive — no energy req

  • simple diffusion 

  • facilitated diffusion

  • osmosis  

• active — req energy 

  • primary 

  • secondary 

• bulk vesicular transport —- large quantities 

  • exocytosis 

  • phagocytosis 

  • pinocytosis 

  • receptor-mediated endocytosis 

diffusion 

solutes will randomly move apart from each other 

high conc→ low conc 

net diffusion rate 

• measures suration at which the conc of sulutes reaches quilibrium across membrane 

• affected by 

  • concentration gradient of solute 

  • permeability of membrane

  • surface area of membrane 

  • temp of solution 

simple diffusion

features

• small , non-polar , hydrophobic, lipid soluble solutes 

  • gases, cholesterol, steroids 

• high→ low conc 

• across permeable membrane 

• no energy expenditure 

rules 

• membrane must be permeable to solutes 

• concentration gradient for solutes must exist across membrane 

facilitated diffusion 

features

• small, charged, polar solutes 

  • ions, glucose, amino acids 

• high→ low conc

• across permeable membrane 

• no energy expenditure 

• must be facilitated by channels (ions) or carriers (polar compounds)

rules

• membrane must be permeable to solutes 

  • depends on presence and activity of channels/carriers 

• conc gradient for solutes must exist across membrane 

mechanism 

• solute attach to binding site on carrier → carrier changes conformation → release solute to other side 

• subject to 

  • specificity 

    • 1 carrier only lets specific things through 

  • competition 

    • solutes want a spot to move 

  • saturation

    • specific to carrier

    • limited number of binding site to polar compounds 

osmosis

diffusion of water molecules across a permeable membrane without the expenditure of energy 

water can slowly diffuse through cell membrane but mainly through aquaporins 

directly influenced by the concentration of the solutes in solution 

rules: 

1. concentration gradient of solutes must exist 

2. the membrane must be impermeable to solutes 

3. membrane must be permeable to water 

water moves from low to high concentration of solutes 

net movement equalizes the dilution of the solutions → total volume of solution increases 

hydrostatic pressure

pressure of water pushing against wall/membrane 

think blood pressure on vessel

osmotic pressure

the minimum amount of pressure required to stope the net movement of solvent

high solute conc difference = high osmotic pressure

higher Osm = higher osmotic pressure

pulling of fluid in

the more water wants to come in → higher osmotic pressure 

tonicity

compares osm of extracellular environment to the osm of the intracellular environment

isotonic 

osmolality is equal 

water moves in and out equally 

ideal environment

hypotonic

Osm of the extracellular environment is less than that of the intracellular environment

water moves into cell→ can cause cell to lyse

hypertonic

osm of extracellular environment is greater than that of the intracellular environment

water goes out → can cause cell to shrivel/crenate

Primary Active transport 

movement of ions/ polar compounds across a permeable membrane from an area of low solute con → high solute conc using carrier proteins with the expenditure of energy (ATP)

carrier protein = enzyme (ATPase) to hydrolyze ATP → ADP+Pi

the energy released by breaking ATP used to drive movement of solutes against conc gradient 

Na+/ K+ ATPase

1. ATPase open to inside and 3 Na+ bind to pump 

2. the binding of the Na+ promotes hydrolysis of ATP → ADP+Pi 

   1. this phosphorylated the pump

3. phosphorylation causes pump to change shape and releases Na+ to outside 

4. 2 K+ from outside binds

5. K+ binding → release of phosphate → returns pump to og position (inside open)

6. ATP attaches and releases K+ and repeat

in all living cells in our bodies 

helps maintain electrochemical gradient for action potentials

• since 3 Na+ out and 2+ in makes the inside more neg 

Secondary Active transport

movement of ions/ polar compounds across a permeable membrane from an area of low solute concentration to an area of high conc using carrier proteins, without direct energy expenditure 

powered by conc gradient created by Na/K ATPase with Na more on the outside

use diffusion energy to move other solutes against their gradients

carrier protein act as co-transporter (symport/antiport) 

Bulk (vesicular transport

movement of large or numerous particles into or out of cell using transport vesicles 

exocytosis - out of cell 

endocytosis - into cell 

• phagocytosis 

• pinocytosis 

• receptor-mediated endocytosis 

Exocytosis 

1. vesicle has a V-SNARE and migrates to meet the PM that has a T-SNARE 

2. V-SNARE and T-SNARE twist 

3. pore opens 

4. contents secreted to outside of cell 

Phagocytosis

cell -eating

only certain cells like WBC can do this 

single large particle being eaten 

1. microbe adheres to phagocyte 

2. phagocyte forms pseudopods that engulf particle 

3. form a phagocytic vesicle containing microbe = phagosome 

eventually fuses w lysosome to make phagolysosome 

Pinocytosis

cell drinking 

large amount of non-specific solutes 

1. PM invaginates and forms a pounch to bring in large quantities of non-specific, small solutes dissolved in extracellular solution 

2. pouch pinches off PM → pinocytotic vesicle 

eventually fuse w lysosome

Receptor-mediated endocytosis

1. extracellular molecules bind to receptors onPM 

2. PM sinks inward and forms a clathrin coated pit 

3. pit pinches off PM and forms clathrin-coated endocytotic vesicle that 

cell signaling function

• growth and development of cell 

• enhance tissue repair 

• facilitate immune activities 

• maintain homeostasis 

types of signaling

local signaling

• paracrine 

  • synaptic

• autocrine

• juxtacrine 

long-distance signaling

• endocrine

Paracrine signaling

local cell-cell communication

signals are released out of cell to nearby target cells

synaptic

• between neurons only

autocrine signaling

self stimulating

regulatory pathway 

juxtacrine 

cell-cell contact 

signal molecule is membrane bound and receptor is on the touched cell 

signal does not go out of cell 

• gap junctions 

• integral proteins 

endocrine signaling

Signal molecules (hormones) secreted into blood to stimulate distant cells

Signal reception

• ligand gated receptors 

• G-protein coupled receptors

transduction of ion channels

• voltage gated ion channel 

• mechanically gated ion channel

Ligand -gated receptors 

1. signal (ligand) binds to ligand-gated receptor 

2. channel opens 

3. ions flow across membrane 

G-protein coupled receptor

1. signal binds

2. G-protein activated

   1. made of alpha, beta, gamma subunits

   2. assembled using GTP

3. one of the subunits breaks off to effector protein or ion channel

4. ion channel opens

5. ions flow across membrane

Hematoxylin + eosin stain

hematoxylin = basic dye

• react w anionic part of cells/ tissues

• dark blue stain that is positive

eosin = acidic dye

• reacts w cationic part

• red/pink stain that is negative

4 primary tissues

1. epithelial tissue

   1. lining of surface or body cavities

   2. glandular secretion

2. connective tissue

   1. support and protect tissues /organs

3. nervous tissue

   1. transmission of nerve impulses

4. muscular tissue 

   1. strong contraction

   2. body movements

zygote

sperm cell fertilizes ovum

eventually develops into 3 embryonic germ layers

3 embryonic germ layers

1. ectoderm (outer)

   1. epidermis

   2. nervous system 

2. mesoderm (middle) 

   1. collagen + fibroblasts in matrix

   2. muscle

   3. bone

   4. blood

   5. cartilage 

3. Endoderm (inner) 

   1. mucus membrane 

   2. digestive 

   3. respiratory system 

Epithelial tissue

• closely adhering cells 

• can have 1 or more cell layers

• avascular 

  • depend on blood vessels of basement membrane for nourishment and waste removal 

• attached to basement membrane (loose CT)

functions: 

1. interacts w external and internal environment of the body 

   1. diffusion

   2. filtration

   3. secretion

   4. absorption 

2. covers body surface and lines body cavities 

3. forms the external and internal linings of organs 

4. constitutes most glands 

what is the surface that interacts the with the outside of epithelial tissue

apical surface

Basement membrane of epithelial cells

• technically a part of the CT

• secreted by the basal epithelial layer 

• anchors epithelium to the CT below it 

consists of

1. basal lamina 

   1. Type IV collagen

   2. laminin + fibronectin adhesive glycoproteins attach to integrins at hemidesmosomes 

   3. proteins and proteoglycans cross-link laminin to collagen network that control porosity of BL

2. reticular lamina 

   1. type III collagen network bound to BL by type VII collagen

identify the parts of this epithelial tissue

H= hemidesmosome 

BL= basal lamina

RL= reticular lamina 

identify the parts of the epithelial tissue 

brown = Basal lamina 

E = epithelium 

Intercellular junction

features

• connections btwn 1 cell and another 

• all cells (except RBC and metastatic cancer cells) are anchored to each other or their matric by intercellular jxns

function

• provide adhesion (resist stress) 

• allow for communication between cells 

• epithelial cells can adhere strongly to neighboring cells 

5 main categories 

1. tight junction (zonula occuludens)

2. adherent junction (zonula adherens)

3. desmosome (macula adherens)

4. hemidesmosome

5. gap junction

Tight junction / zonula occludens

• region where adjacent membranes sealed together by linker proteins (transmembrane proteins) making a lateral perimeter around cell

  • claudin

  • occludin

• closest to apical surface

Functions

• seals off space between cells to prevent compounds from passing between instead of through the cell 

• restricts movement of membrane lipids and protein of apical surface to other areas of cell 

issues: 

• toxin from food poisoning bacteria binds to claudin and weaken tight junctions and allows tissue fluid to leak into intestinal lumen

what kind of intercellular jxn is this 

tight junction 

• close to apical surface

Adherent junctions / zonula adherens

• region where adjacent cells are bround together by transmembrane proteins (cadherins) in the presence of Ca2+

• on cytoplasm side: 

  • cadherins bound to catenin proteins which link actin filaments to form terminal web

• creates lateral perimeter

function 

• stabilize and strengthen zonula occludens/tight junctions 

Desmosomes/ macula adherens 

• Transmembrane proteins (desmoglein+ desmocollins - part of cadherin fam) join neighboring cells together 

• cytoplasmic side: 

  • desmoglein+desmocollins  are bound to thick plaque protein which are linked to intermediate filaments 

function: 

• resist mechanical stress to keep cells from pulling apart 

what kind of intercellular junction is this 

desmosome 

Hemidesmosomes

• transmembrane protein= integrins , attach to laminin in BL of basement membrane

• on cytoplasmic side: integrins bound to plaque proteins which are linked to intermediate filaments 

  • intermediate  filaments link hemi-hemi-desmo

function

• anchor the basal surface of cells to basement membrane

identify the structures 

MV= microvilli

TJ= tight junction

AJ= adherent junction 

D = desmosome 

IF = intermediate filament 

Gap junctions

• 6 transmembrane proteins (connexin) arranged next to each other → form aqueous channel (connexon) that connects lateral surfaces of neighboring cells 

function: 

• allow ions, glucose, polar compounds, amino acids, water, and other small (<1.5 nm) solutes to pass from one cell to another 

• rapid cell to cell communication 

• can open and close and is tightly regulated 

what kind of intercellular junction is this + what microscope 

gap junction 

atomic force 

compare simple epithelium and stratified epithelium

simple:

• 1 layer of cells

• named by shape of cells

• all cells attached to basement membrane

stratified

• more than 1 layer of cells

• named by shape of apical layer

• some cells rest on tope of others and are not attached to the basement membrane 

epithelial cell shapes

1. squamous

   1. oval and flattened nucleus

   2. flat shaped cell

2. cuboidal

   1. width=height

   2. round + central nucleus

3. columnar

   1. tall>wide

   2. nucleus stretched vertically and closer to basal surface

epithelial cell classes

1. simple

   1. 1 layer

2. pseudostratified columnar

   1. technically 1 layer, but looks like multiple

3. stratified

   1. multiple layers

simple squamous epithelium

• single row of squamous cells attached to basement membrane

• found in serous and synovial membranes

  • serous: surrounds organs + makes serous fluid

  • synovial: joints + synovial fluid

  • secrete fluid that lubricate tissue

• locations

  • lungs (alveoli)

  • kidneys (glomerulus + tubules)

  • internal layer of BV (endothelium)

• functions

  • rapid diffusion, filtration, absorption of gases, nutrients, wastes

what kind of epithelium is this 

simple squamous 

what kind of epithelium is this made of

simple squamous - lungs /alveoli

what kind of epithelium is this made of 

simple squamous - BV

simple cuboidal epithelium

• single layer of cuboidal cells attached to basement membrane 

• found as secretory cells of exocrine and endocrine glands 

• tubes and ducts usually = cuboidal 

  • minor ducts = simple cuboidal 

  • major ducts = stratifies cuboidal 

functions

• diffusion 

• reabsorption 

• secretion 

locations

• collecting tubules of kidneys

• thyroid follicles

• outer surface of ovaries 

• salivary glands

• simple ducts

what kind of epithelium are these 

simple cuboidal