MODULE 5: epithelial cells Flashcards
types of epithelial cells (8)
- simple squamous
- single layer
- lungs, kidneys - simple cuboidal
- single layer, cube-shaped
- thyroid gland, kidney, salivary glands, pancreas - simple columnar
- single layer, column-shaped
- gallbladder, stomach, small intestine - stratified squamous
- 2-6 layers
- cells at bottom differentiate and move to top
- lip, vagina, skin - stratified cuboidal
- ducts of sweat glands - stratified columnar
- salivary gland - pseudostratified columnar epithelium
- looks like multiple layers but not all cells attached to basement membrane
- trachea - transitional epithelium
- 2-6 layers of different shapes
- can expand and shrink
- bladder
gap junctions
- two connexons (6 monomers - connexins) stacked end to end
- exist in open or closed conformation
- allow signals to pass between epithelial cells
adhering junctions (adherens)
- found in top apical region
- adherens responsible for maintaining epithelial structure
- actin filaments maintain structure of adherens
- catenins bind actin filaments to cadherin dimers
- cadherin dimers attach to membranes of two cells
desmosomes
- below adherens but above gap junctions
- connect intermediate filaments to maintain cell architecture
- desmosomes attach keratin but cadherin still adheres two membranes
- attachment plaque made up of proteins. sticky plaques allow attachment of other important proteins e.g. keratin
- diseases associated with mutations in attachment plaque
hemi-desmosomes
- half desmosome
- similar tissue integrity/function as desmosomes but different proteins in attachment plaques
- distributes forces along epithelial cells
tight junctions
- most apical
- functions as barrier between apical and basal domains
- maintains cell polarity
- —> - constrain diffusion
- —> selective gates
- clausins are the structural element
focal adhesions
- found on cytosilic side of basement membrane
- proteins protrude through plasma membrane to basement membrane = INTEGRINS
- these integrins bind to structural proteins
- contain proteins which help attach actin filaments
Na+/K+ pump cycle
- sodium binds to intracellular binding site
- ATP hydrolysed - ADP leaves and phosphate group remains
- conformational change
- sodium released into extracellular space
- extracellular potassium binding site exposed
- potassium binds, phosphate leaves and ATP binds
- conformational change
- potassium enters cell
highly important role in osmotic equilibrium
anatomy of kidney
kidney is highly vascular
made of cortex and medulla
cortex contains functional unit of kidney called nephron
nephron:
- bowman’s capsule
- proximal convoluted tubule (PCT)
- henle’s loop
- distal convoluted tubule (DCT)
- cortical convoluted tubule (CCT)
glomerulus
contained within renal corpsucle
podocytes filter large molecules like proteins
foot processes —> only small ions and glucose can filter through into lumen to be secreted as urine
proximal convoluted tubule (PCT)
- function
- sodium recovery
- glucose recovery
- water transport
function: recovers fluid and solutes from glomerular filtrate, prevents kidney from excreting blood plasma
contains leaky tight junctions on apical membrane —> interstitial fluid can flow back to the blood
sodium recovery:
- na+ enters via Na+/H+ exchanger (na in H+ out)
- protons pumped out —> cells not acidic
- carbonic anhydrase (CA) produces protons via CO2 and H2O —> HCO3-
- HCO3- & Na+ cotransporter on basal membrane
glucose recovery:
- must reabsorb 100% of glucose in urinary filtrate to power brain
- early proximal tube absorbs most glucose via cotransporter SGLT2
- —> Na+ in, energy drags in glucose
- —> glucose reabsorbed into interstitial space via GLUT2 = glucose transporter
- late proximal tubes absorbs 2% glucose
- —> absorbs glucose via SGLT1
- —> glucose reabsorbed into interstitial space via GLUT1 = glucose transporter
water transport:
- water absorbed via leaky tight junctions and aquaporins
distal convoluted tubule (DCT)
- sodium recovery
sodium recovery:
- atp-ase drives sodium and potassium against concentration gradients using ATP
- potassium channel on basolateral side
- na+ enters cell via ENaC channel on apical membrane
glucose recovery in diabetes
diabetes = high glucose in blood
glucose filters through foot processes —> high glucose in blood
glucose transporters (SGLT) become saturated —> can’t absorb any more glucose —> glucose secreted into urine
excess glucose can cause toxicity
drugs inhibit SGLT1/2 to lower blood glucose and promote urinary excretion
water cycling in collecting duct: aquaporin 2
low water intake —> signalling cascade —> vesicle with many aquaporins fuses with plasma membrane —> reabsorb more water —> concentrated urine
happens in reverse with high water intake —> vesicle pinches off —> less reabsorbed —> dilute urine
epithelial cells in the lung
control osmotic gradient to regulate fluid movement (increase gradient = more movement)
ions/water move from basolateral side and secreted to create fluid
Cl- movement very important
Cl- ions enter via Na+/Cl-/K+ co-transporter on basal membrane
also have Na+/K+ ATPase —> sodium can move back out into interstitial space
Cl- exits via CFTR channel on apical membrane
no CFTR —> only some movement of Cl- into airway fluid
sodium reabsorbed from fluid —> no inhibition anymore —> secreted back into interstitial space via Na+/K+ ATP-ase
excess reabsorption of sodium + no movement of Cl- —>large number of ions in airway fluid —> causes movement of water back into interstitial fluid —> fluid becomes sticky and can’t be moved
defective CFTR —> cystic fibrosis —> dehydrated mucus in lung —> blockages —> airway obstruction etc
absorption in the GI tract
- mucosa (epithelial membrane) remains same throughout entire small intestine
- villus (folds) increase surface area
- small intestine contains many different specialised cells
absorption of carbohydrates:
- SGLT1 (sodium glucose transporter) allows cotransport of sodium and glucose into cell
- GLUT2 —> facilitated diffusion of glucose into blood, fructose moves out of cell
- GLUT 5 —> fructose can move into cell
acid secretion on the stomach
G-cells regulate amount of acid secreted
in parietal cells:
- Cl- enters via Cl- channel & NKCC1 co-transporter on basal membrane
- Cl- driven into lumen via CFTR
- Water enters via aquaporin
- Protons pushed out into lumen via H+/K+ pump (K+ also moves in)
- Bicarbonate must be removed via bicarbonate/Cl- anti-porter
- Na+/K+ ATPase to drive chemical gradient and MP
parietal cells increase surface area —> increase number of pumps —> increase acid secretion
ion transport in the pancreas: acinar cells
- Na+ exits via Na/K+ pump on basal side
- Na+ gradient drives Cl- into cell via Na/K/Cl symporter
- K+ driven out by gradient via K+ channels on basal side
- Cl- driven into lumen via Cl- channels on apical side
duct cells: - Cl- movement into lumen drives Na+ movement into lumen via leaky tight junctions (bidirectional)
- Water also moves through tight junctions (bidirectional)
- increase in calcium via hormonal and neural input —> UNIQUE TO ACINAR CELLS
ion transport in the pancreas: duct cells
- CO2 enters via
- H+ exits via proton pump
- H+ exits & Na+ enters via anti-transporter
- sodium enters
- sodium potassium pump
- K+ and Ca2+ exit via transporter involving cAMP
- C;- exits via channel on appical side
- bicarbonate exits via CFTR as well at Cl-
- bicarbonate exits via antiporter —> Cl- enters
- H2O and sodium through leaky tight junction
secretion from the pancreas
duodenum lined by epithelial cells
ductal cells line pancreas
CCK binds receptor in acinar cells —> increase release of digestive enzymes
secretin binds receptor on ducts —> increases bicarbonate fluid secretion
mechanisms of calcium signalling
Ca2+ intracellular level determined:
- ON –> release from inernal stores
- OFF –> calcium exits via antiporters or exchangers –> calcium can also bind mitochondria
ON:
- VG ion channels / receptor-operated channels / second messenger operated channels allow influx of Ca2+
- release regulated by IP3 (binds calcium directly) and RYRs (binds large complexes)
OFF:
- ATPase / Na+/Ca2+ exchanger / SERCA / mitochondrial uniporter control off mechanism
- important for homeostasis
calcium signalling in wound repairs - darier disease
calcium used to detect stress mediated damage
calcium allows mediators via exocytosis to initiate proliferation and migration —> close wound
darier disease:
- skin disorder –> less adhesion between cells
- loss of function mutation in SERCA2 encoding gene
- SERCA removes Ca2+ in “off” reaction
- low Ca2+ concentration in ER
- results in loss of tight junctions and desmosomes –> no cell polarity –> no cell-cell contact
