Download Histology - take homes from lectures 2012

Histology lectures 2012 – Main ideas/notes
Blood
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Hematocrit – percentage of blood volume that is cells, should be between 35%-50%
Albumin – carrier protein, most of plasma proteins, responsible for colloid osmotic pressure
Fibrinogen – largest plasma protein, produced in liver, transformed into fibrin for clot formation
Platelet granules
o α-granules – contain fibrinogen, coagulation factors, plasminogen, plasminogen
activator inhibitor, platelet-derived growth factor – initial phase of clot formation
o δ-granules – platelet adhesion and vasoconstriction of injured area, contain ADP, ATP,
histamine, and serotonin
o γ-granules – contain hydrolytic enzymes, clot resorption during repair
Dendritic cells – eat invaders and put their antigens on their own surface to draw attention to
the fact that it caught an invader – body decides whether or not to develop specific response
WBC’s
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Neutrophils – first responders, will phagocytose and digest
o Roll along with selectins
o Integrins say stop rolling
o Heparin and histamine open an intracellular junction for them to come out through
o Primary, secondary, and tertiary granules
o Bands – immature neutrophils
o Segs – mature neutrophils
Eosinophils – spew their contents at invaders, used for allergic reactions, parasites, and chronic
inflammation
o Primary and secondary granules
Basophils – least of leukocytes, has primary and secondary granules, has Fc receptor on PM that
attaches to IgE to label an invader as “destroy me”
Lymphocytes – main functional cells of immune system, differentiate into:
o T cells – mature in thymus, adaptive immunity, phagocytose invaded and infected cells
(also cancer cells)
o B cells – mature in bone marrow, adaptive immunity, further differentiate into plasma
cells that spew antibodies all over invader
o NK cells – innate immunity, programmed to kill certain virus-infected cells and tumor
cells
Monocytes – migrate from bone marrow to tissues, once they enter the tissues, they’re called
macrophages, phagocytose and degrade antigens and then present them to T cells
Hemopoiesis
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Formation of blood
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All blood cells (erythrocytes, leukocytes and thrombocytes) form and develop in red bone
marrow
Lymphocytes can also be made/raised in lymphatic tissues
Kidneys
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Outer layer of capsule – DCT with fibroblasts and collagen
Inner layer of capsule – LCT with myofibroblasts
Capsule continues around towards hilum, where it covers renal sinus, and then becomes
continuous with connective tissue of the calyces
Parts of nephron that are in medulla are in renal pyramids
Blood supply – renal artery  interlobar artery  arcuate artery  interlobular artery 
afferent artery
Every 10 years after age 50, you lose 10% of your nephrons
Glomerular basement membrane made of type IV collagen, proteoglycans, and multiadhesive
proteins
o Has endothelial cells and podocytes
o Lamina rara externa, lamina densa, and lamina rara interna
Mesangial cells – phagocytosis and endocytosis of trapped proteins in podocytes’ foot
processes, provide structural support where there is no GBM, and allow for distension
modulation with higher BP
Parietal layer of Bowman’s capsule – squamous epithelium
Juxtaglomerular apparatus – consists of juxtaglomerular cells, extraglomerular mesangial cells,
and macula densa
o Juxtaglomerular cells – adjacent to afferent arteriole, regulates BP through reninangiotensin-aldosterone system
o Macula densa – monitors Na+ concentration of the tubular fluid, regulates both the
glomerular filtration rate and release of renin from juxtaglomerular cells
Proximal convoluted tubule – brush border, plicae, junctional complex (tight junctions and
zonula adherens), basal striation (mitochondria oriented vertically along basal membrane)
o Contain Na+/K+-ATPase pumps and AQP-1
o Microvilli are covered in glycocalyx, which contains ATPases and peptidases, allowing for
reabsorption of amino acids, sugars, and polypeptides
o Proteins and large polypeptides endocytosed
o Adjusts pH of urine by absorbing HCO3- and releasing organic acids and bases as needed
Proximal straight tubule – cuboidal cells, brush border, lumen contains precipitate
Loop of Henle – thin segments
o Descending – water out
o Ascending – salt out – epithelial cells produce uromodulin (influences NaCl
reabsorption)
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Distal straight tubule – part of medullary ray, Na+ actively transported (Na+/K+ ATPase pump),
while Cl- & K+ diffuse through respective channels, some K+ leaks back into lumen creating +
charge and drives reabsorption of Ca2+ and Mg2+, cuboidal cell lacking brush border
Distal convoluted tubule – Na+ out, K+ in, HCO3- out, H+ in, NH4+ in
o Has macula densa
o Aldosterone stimulated by angiotensin II increases reabsorption of Na+ and secretion of
K+
Collecting tubes and ducts – run down renal columns, squamous to cuboidal and transition to
columnar near renal papilla
o Light cells – contain ADH-regulated AQP-2 channels
o Dark cells – secrete H+ (α-intercalated cells) or HCO3- (β -intercalated cells)
 Number decreases as you travel down the collecting tube until there are none
at the renal papilla
Area cribrosa  renal papilla  minor calyx  major calyx  renal pelvis
Urinary System after Leaving Kidneys
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Look for dome-shaped cells that project into lumen to classify urothelium
2 layers of smooth muscle (inner longitudinal, outer circular) except at ends of ureters
Detrusor muscle – smooth muscle of bladder
Uroplakins – folds of epithelial cells that allow bladder to expand as it fills
Sensory fibers from bladder travel to Sacral cord, afferents of micturition reflex
Urethra – urothelium  pseudostratified columnar  stratified squamous (continuous with
outside skin around urethral opening
o Prostatic urethra – ejaculatory ducts enter here, urothelium
o Membranous urethra – pseudostratified columnar, surrounded by erectile tissue
o Penile urethra – stratified squamous
Endocrine System
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3 types of hormones
o Steroids – cholesterol-based (estrogen, testosterone, etc.), transported via plasma
proteins
o Small peptides – dissolve in blood or have plasma proteins (specific), (insulin, glucagon,
GH, oxytocin)
o Amino acids and arachadonic acid derivatives – synthesized by neurons and adrenal
medulla (prostaglandins, thyroid hormones, etc.)
Pituitary Gland – sits in sella turcica of sphenoid bone, attached to hypothalamus by
infundibulum
o Anterior pituitary – forms from ectoderm of oropharynx
 Pars distalis – most of “anterior pituitary”
 Pars intermedia – has colloid-filled follicles (don’t know why)
 Pars tuberalis – forms sheath around infundibulum
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Posterior pituitary – forms from neuroectoderm of 3rd ventricle
 Pars nervosa – neurosecretory axons and their endings (bodies in
hypothalamus)
 Infundibulum – continuous with median eminence and contains
hypothalamohypophyseal tracts
Superior hypophyseal arteries – supply pars tuberalis, infundibulum, and eminence –
arise from internal carotid and posterior communicating artery of Circle of Willis
Inferior hypophyseal arteries - supply pars nervosa, arise from internal carotid
Posterior pituitary is under direct neuronal control from hypothalamus, and anterior
pituitary controlled by hypothalamic-hypophyseal portal system (inhibitors and
stimulators that are sent down it)
Anterior pituitary produces its own hormones, but posterior pituitary just stores (in
neurosecretory vesicles) and releases hormones made by neuronal cell bodies in
hypothalamus
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o Pituicytes – supportive cells like astrocytes in posterior pituitary
Hypothalamus – MAJOR controlling center of ANS and endocrine system
o Makes and secretes releasing hormones, somatostatin, dopamine
Pineal gland – midline of brain
o Pinealocytes – make melatonin
o Interstitial glia – “astrocytes” of pineal gland
o Calcified “brain sand” accumulates here
Thyroid – develops during 4th week of gestation from endodermal lining of the floor of primitive
pharynx – by 9th week, starts forming thyroid follicles (functional unit) and by 14th week, the
follicular cells start to contain colloid
o Follicular cells (principal cells) – surround colloid bubbles and produce T3 and T4
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Make their hormones from pieces and iodide in blood, put them in colloid
bubbles to store, then bring them out of colloid bubbles and into circulation
when needed
o Parafollicular cells (C cells) – do not touch colloid bubbles and produce calcitonin
o T3 and T4 regulate heat production and basal metabolism and play important role in
neural and body tissue growth in fetus (why mother needs to not be hypothalamic)
 Stimulates gene expression for GH
o Calcitonin – decreases blood Ca2+ by reabsorbing it into bones
Parathyroid glands – 2 superior and 2 inferior that form from 3rd and 4th branchial glands
(switched from obvious pairing)
o Oxyphil cells – differentiate during puberty, no known secretory role
o Principal cells (chief cells) – differentiate during embryological development, stimulated
by changes in Ca2+ in blood stream – produce PTH (raises blood calcium levels by
resorbing bone)
Adrenal glands – embedded in perirenal fat (hard to find)
o Cortex – secretes steroids – from mesoderm
 Zona glomerulosa – outer layer filled with fenestrated capillaries – makes
mineralocorticoids for sodium, potassium, and water homeostasis – under
control of renin-angiotensin-aldosterone system
 Zona fasciculata – middle layer (thickest layer) that makes glucocorticoids that
can convert norepinephrine to epinephrine, enable fatty acid and glucose
uptake and breakdown, reduces rate of glucose use and oxidation of fatty acids,
also depress immune and inflammatory responses
 Zona reticularis – thinnest layer (inside layer) makes weak androgens and DHEA
o Medulla – secretes catecholamines – from neural crest cells
 Chromaffin cells – innervated by SNS, can be activated to release by ACh
 Large vesicles – secrete norepinephrine
 Small vesicles – secrete epinephrine
 Makes sympathomimetic (fight or flight)
Endocrine pancreas – islets of Langerhans
o α-cells – secrete glucagon (releases glucose into bloodstream)
o β-cells – secrete insulin to take up glucose by synthesizing glucagon
o δ-cells – secrete somatostatin that inhibits both of the previous 2 actions
Accessory Digestive Organs
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Exocrine Pancreas – produces zymogens and releases them into ducts
o Cells of intercalated ducts (centroacinar cells) secrete bicarbonate and water when
stimulated by secretin (made by APUD)
o Acinar cells stimulated by CCK (made by APUD)
o Pancreatic polypeptide – made by F cells of pancreatic islets – inhibits digestive
elements and relaxes gallbladder
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Pancreatic juices contain amylase, trypsin, chymotrypsin, carboxypeptidase, DNAse and
RNAse, lipases, and cholesterol esterase
o Controlled by vagus nerve as well as hormonal stimulation
o Reasons digestive juices don’t digest pancreas
 Produced in zymogen format
 Work better at basic pH and kept in vesicles at low pH
 Packaged in vesicles
 Presence of trypsin inhibitor (trypsin needed to activate all other digestives)
Liver – Glisson’s capsule covers all 4 lobes (right, left, caudate, and quadrate)
o Develops embryologically from outpocketing of foregut (hepatic diverticulum)
o Secretes somatomedins in response to GH
o Synthesizes angiotensinogen
o Conjugates bilirubin and excretes it in bile
o Carbohydrate metabolism, lipid synthesis (lipoproteins, phospholipids, and cholesterol),
and protein synthesis (plasma proteins and clotting factors)
o Converts drugs to lipophilic metabolites and releases them through bile for excretion
o Flow of blood and bile in opposite directions
o Portal space (space of Kiernan) – between hepatic lobules and have portal triads at their
intersections
o Space of Disse – surrounds sinusoids (capillaries in actual hepatocyte)
 Contains Kupffer cells that eat bacteria and dead RBC’s and recycle heme
 Have pit cells – NK type cells that kill tumor cells after activation with interleukin
2
 Have hepatic stellate (Ito) cells that store vitamin A – if damaged, they produce
collagen, causing cirrhosis
o Bile continuously made by hepatocytes and transported by canaliculi to bile ductule in
portal space
Gallbladder – it and cystic duct develop from hepatic diverticulum of embryo
o No submucosa o Simple columnar epithelium
o R-A crypts
o R-A sinuses – go down into muscularis externa – shows pre-pathological signs
o Na+/K+-ATPase pumps pump out ions and water follows, concentrating bile
Sphincter of Oddi – stimulated to open by NO or VIP, guards major papilla opening of duodenum
Gallstones – can be yellow (cholesterol) or pigmented (calcium bilirubinate)
Causes of jaundice
o Too much bilirubin – liver cannot process it all
o Inability of liver to conjugate bilirubin (through defect)
o Blockage of bile ducts (cancer of head of pancreas, gallstones, etc.)
Lymphatic System
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Lymph dumps into junction of left subclavian and internal jugular veins
Blind-ended tubes in capillary beds that go through nodes, eventually end up in thoracic duct
and dump as described above into blood stream
Lymph capillaries are endothelium with discontinuous basal lamina (more permeable to proteinrich fluid)
Lymphatic vessels have valves to maintain one way direction
Immunocompetent – can see an antigen (not necessarily currently reacting to it, but can see it)
Immune responses
o Innate – non-specific protectors, no memory, immediate response
o Adaptive – specific for each antigen, delayed response time, has memory
 Humoral – antibody-mediated
 Cellular – direct cell mediation
If lymphocytes don’t find their antigen, they will die
CD8+ T cells – actual cell destroyers – kill virus infected cells – cause targets to undergo
apoptosis
CD4+ T cells – helper T cells – help B cells produce antibodies and phagocytes destroy
intracellular pathogens
Antibodies – 2 heavy chains and 2 light chains
blue is heavy
red is light
NK cells release perforins and granzymes to kill target cells
Lymphocytes mature in bone marrow, GALT (tonsils, adenoids, appendix, etc.), and thymus
(antigen independent environment)
Antigen-dependent activation of antigen recognition – lymphocytes make effector lymphocytes
and memory cells (about 4-6 days from antigen recognition to returning activated lymphocytes
to bloodstream)
Germinal centers – dense, spherical structure formed by B-cells that have recognized antigen
and are actively proliferating
T cells and B cells are racist against each other in a lymph node (separate)
Primary lymph nodule – small lymphocytes gathered
Secondary lymph nodule – has corona of small lymphocytes (mantle layer) and germinal center
in middle of lymphocyte proliferation, plasma cell differentiation, and antibody production
Lymph nodes – actually encapsulated lymph centers (these are the beads on the lymph system’s
strings) – have cortex and medulla – trap APC’s, macrophages, and antigens – T cells in
paracortical areas, and B cells in follicles (which can have germinal centers)
o Have afferent (bring lymph to node) and efferent lymph ducts
o Capsule – DCT surrounding node
o Trabeculae – DCT framework
o Reticular tissue – supporting meshwork within the organ, reticular cells and fibers
o Cortex – has
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Superficial (Nodular) Cortex - dense outer portion that consists of aggregations
of lymphocytes organized as nodules
 Deep Cortex – no nodules, contains most of the T cells in the lymph node
(thymus dependent cortex)
o Medulla – has
 Made of cords of lymphatic tissue (contains B-cells, macrophages, DCs and
plasma cells) separated by medullary sinuses
 Sinuses converge near hilum, drain into efferent lymphatics
o Lymph node sinuses – for filtration of lymph – macrophages stick processes in there to
filter out antigens and stuff
 Subcapsular (Cortical) Sinuses – between capsule and cortical lymphocytes
 Trabecular Sinuses – Originate from subcapsular sinus, pass through cortex
along trabeculae
 Medullary sinuses – medulla, trabecular sinus drains into it
o High Endothelial Venules (HEV’s) – postcapillary venules, located in deep cortex
 Concentrate lymph by transporting fluid and electrolytes from afferent vessels
to bloodstream
 Most lymphocytes (90%) enter lymph nodes via HEVs, remainder via afferent
lymphatics
 Express receptors for activated B and T-cells, leave bloodstream for lymph node
by diapedesis
Reticular cells make type III collagen for support (look like dendritic cells)
Follicular dendritic cells – dendritic cells in germinal centers – bind antigen-antibody complexes
on Fc receptor on surface – engulf and display for B cell recognition
Thymus – mostly replaced by adipose tissue by puberty but can be restimulated under
conditions that demand rapid T-cell proliferation – inner structure is like a giant lymph node
o Blood-thymus barrier – keeps T cells away from anything else so they don’t have that as
their programmed site to attack
o Epithelioreticular cells – have features of epithelial cells and reticular cells
Spleen – mostly for RBC garbage disposal but can take up antigens too
o Red pulp – for RBC disposal
o White pulp – lymphocytes surrounding arterioles
 Periarteriolar lymphoid sheath (PALS) – contains T cells
 B cell corona – surrounds germinal centers
o All the blood goes through the central artery and it just ends in the red pulp (after
several branches) – blood goes through splenic cords for filtration and returns through
splenic sinuses
o Splenic cords – red pulp, loose meshwork of reticular cells and fibers, contain
erythrocytes, lymphocytes, and other immune cells
o Splenic sinuses – red pulp, lined by endothelial cells with large spaces, surrounded by
basal lamina loop
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Open circulatory system allows for maximum exposure of blood to macrophages in
cords before it is allowed to go back to circulation
Those without spleen are slightly more susceptible to blood-borne pathogens, but
otherwise they are just fine
Heart
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Endocardium – innermost layer, composed of endothelial cells, connective tissue, and smooth
muscle cells, conduction system of the heart (Purkinje fibers) is located here
Epicardium – visceral layer of serous pericardium
Base of fibrous pericardium attached to central tendon of diaphragm and anterior connected to
sternopericardial ligaments
Pericardial cavity – lined by mesothelial cells (squamous) that produce serous fluid to reduce
friction during contraction
Heart valves
o Spongiosa – LCT with loosely arranged collagen and elastic fibers – dampens vibrations
of valve closure
o Fibrosa – core of valve – fibrous extensions of DCT from skeletal rings
o Ventricularis – covered with endothelium, many layers of DCT and elastic fibers
 In AV valves, this is continuous with chordae tendinae
Cardiac SNS and PNS Influence
o SNS – T1-T4, synapse in cervical ganglia, innervates coronary arteries, which secrete
norepinephrine, causing tachycardia
o PNS – vagus nerve (CN X), innervates coronary arteries, which secrete ACh to cause
bradycardia
Norepinephrine and epinephrine activate β1 receptors, causing inotropic effect (increased force
of contraction) and chronotropic effect (increased rhythm)
Arteries and Veins
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Vasa vasorum and nerva vascularis – blood vessels and nerves that supply large arteries and
veins
Tunica intima
o Endothelium – squamous cells with long axis pointing in direction of blood flow
 Maintain selective permeability and non-thrombogenic barrier, modulates
blood flow, regulates immune response, hormonal synthesis and metabolic
activities, modification of lipoproteins (oxidation by free radicals, which are
endocytosed by macrophages that become foam cells of atheromatous plaques
of atherosclerosis)
 Von Willebrand factor – prothrombogenic substance released by DAMAGED
endothelium
 Sheer stress causes release of NO, which causes vasodilation
o Basal lamina
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o subendothelium
Tunica media – smooth muscle – hypertension caused by thickening of this layer in response to
increased need for more smooth muscle
Tunica adventitia
Capillaries only have endothelium
Pericytes – surround continuous capillaries and respond to NO to provide vascular support and
promote stability through physical and chemical signaling with endothelium
Post-capillary venule – have more pericytes than capillaries, primary site of histamine and
serotonin secretion, cuboid cells
Pericytes go away when you reach “small vein” stage
Medium veins have valves to prevent backwash
Large veins – vena cavae, portal vein, and subclavian – tunica adventitia also has longitudinally
oriented smooth muscle
Digestive System
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Alimentary canal has 4 layers
o Mucosa
 Epithelium
 Lamina propria
 Muscularis mucosa
o Submucosa – has Meissner’s plexus that controls contraction of muscularis mucosa
o Muscularis externa
 Inner circular
 Outer longitudinal
 Auerbach’s plexus runs between these two layers and innervates both – enteric
neurons (neither PNS nor SNS)
o Adventitia (attached to other organs) or serosa (free)
 Simple squamous epithelium
 Adventitia is mesothelium and serosa is continuous with visceral peritoneum
Salivary amylase from parotid gland begins digestion of carbohydrates in mouth
Salivary lipase from Von Ebner’s gland in the tongue begins digestion of lipids in mouth
Cells in glands of mucosa of stomach
o SCAMP – SAM in all, but C and P only in fundic (body)
 Stem cells
 Chief cells – secrete pepsinogen, gastric lipase, and renin
 APUD – enteroendocrine cells
 Mucous cells – secrete mucous
 Parietal cells – secrete HCl and intrinsic factor (necessary for B12 absorption)
Cardiac stomach – short gastric pits that can curl back on themselves
Fundic stomach – deep, tubular branched gastric pits
Pyloric stomach – glands do not extend beyond muscularis mucosa
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Pernicious anemia – B12 deficiency
o B12 taken up in ileum and stored in liver until needed
o B12 needed for proper formation of RBC’s
Zollinger-Ellison syndrome – gastrin-secreting tumor that leads to ulcer because of increased HCl
production by parietal cells in response to the excess gastrin
Small intestine – increasing number of goblet cells and decreasing number of villi as you go
down toward large intestine
o Plicae circularis – 3x absorption SA – core of submucosa
o Villi – 10x absorption SA – core of mucosa
o Microvilli – 20x absorption SA – core of actin filaments
APUD hormones
o Serotonin, substance P, VIP – increase motility by contraction and relaxation of muscle
o Secretin – increase bicarb and water secretion of pancreas (neutralizes duodenum)
o Gastric inhibitory peptide – inhibits gastric acid secretion in small intestine
o CCK – pancreas releases enzymes and gallbladder releases bile
o Somatostatin – EVERYBODY STOP NOW!!!
Duodenum – has goblet cells (secrete mucous) and Brunner’s glands (secrete alkaline mucous)
o Has Panneth cells – secrete lysozyme
o Has M-cells (APC’s)
o Bile from liver emulsifies fats to allow absorption and passage
o Large lipids go in lacteals (lymph vessels in villi) – rER gives it a protein coat (making it a
chylomicron) which then goes into lymph system (thus goes through liver on second
time through system)
o Peptides, carbs, and small lipids absorbed in blood stream to go to liver for processing
Jejunum – large plicae circularis
Ileum – Peyer’s patches
Vermiform appendix – off of cecum – Peyer’s patches and crypts but no villi or teniae coli
o Identify this section with crypts of Lieberkühn
Colon – outer longitudinal layer modified to be teniae coli – have enterocytes, goblet cells,
APUD, and stem cells – more goblet cells as you get closer to the exit lane
Crohn’s Disease – involves entire wall – skip lesions – cobblestone appearance and string sign
Ulcerative colitis – entire circumference of affected area ulcerated in mucosa and submucosa
Respiratory System
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Nasal cavity – stratified squamous – sebaceous glands and vibrissae
o Posterior part of vestibule marked by change from stratified squamous with sebaceous
glands to pseudostratified columnar without sebaceous glands (respiratory epithelium)
Cells of respiratory epithelium of upper tract
o Goblet cells – secrete mucous
o Brush cells – have small microvilli for receptors (afferent nerve fibers on basal surface)
o Basal cells – respiratory stem cells
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Granule cells – contain numerous dense granules and control serous and mucous
secretions
Respiratory epithelium trends
o Deeper you go, thinner the epithelium (columnar, cuboidal, squamous)
o Deeper you go, less goblet cells you find
o Cilia disappear in alveoli (but not before)
Kartagener’s syndrome – lack dynein, so cilia don’t work and mucosal escalator is dead
Olfactory Cells
o Olfactory receptor cells (ORCs) – neuron axons – form cranial nerve I
o Supporting cells – columnar cells that provide mechanical and metabolic support for
ORCs
o Basal cells – become new ORCs
o Brush cells – microvilli receptors
o Bowman’s (olfactory) glands – release proteinaceous secretion (olfactory cleanser and
solvent)
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Na and Ca2+ channels in ORCs activated by cAMP
Eustachian tube connects to pharynx
Cartilages of larynx
o Epiglottis
o Arytenoid – involved with vocal cord movement
o Thyroid – Adam’s apple
True vocal cords (vocal folds) – stratified squamous epithelium, contains vocal ligament and
vocalis muscle
Ventricular folds (false vocal cords) – ciliated pseudostratified squamous epithelium and have
serous glands in the lamina propria
Rima glottids – sides of true vocal cords
Trachea has mucosa, submucosa, cartilaginous layer (C-shaped rings), and adventitia
Smokers have thicker basement membrane in tracheal mucosa than normal people – from
smoker’s cough
Basement membrane of tracheal mucosa normally has lymphocytes, mast cells, eosinophils, and
fibroblasts
Tracheal submucosa is LCT and has vessels and lymphatics
Trachealis muscle between adventitia and submucosa – where tracheal cartilage rings are not
Adventitia of trachea contains largest vessels and lymphatics
Bronchi have cartilaginous plates, not C-shaped rings
Bronchi have mucosa, muscularis (circular layer of smooth muscle), submucosa, cartilaginous
plates, and adventitia
Becomes a bronchiole when it is less than 1 mm
Terminal bronchioles
o Large terminal bronchioles – goblet cells, ciliated pseudostratified columnar
o Small terminal bronchioles – simple cuboidal, no goblet cells, have Clara cells
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Clara cells – dome-shaped apical surface, secrete lipoprotein that prevents
luminal adhesion should airway collapse during expiration
Alveolar cells
o Brush cells – neuroreceptors monitoring air quality
o Type I alveolar cells – where gas exchange happens
o Type II alveolar cells – make surfactant
o Dust cells – macrophages that eat dust, dirt, smoke, whatever comes in there (some
remain for life and can be seen as black splotches in autopsy, but some do make it up
ciliated excalator)
Pores of Kohn – openings in interalveolar septa allowing communication of air between alveoli
Surfactant proteins
o A – homeostasis, immune response to fungi, bacteria, and virus (A game)
o B – adsorption and spreading of surfactant (butter)
o C –just an inanimate layer
o D – defense and binding microorganisms
Emphysema – less SA for gas exchange, body compensates by hyperventilation, but blood gases
relatively normal (“pink puffer”)
Chronic bronchitis – capillary bed damaged, so cannot get sufficient gas exchange and must
breathe in before last breath has completely been expired (“blue bloater”)
Pneumonia – in response to viral or bacterial infection
o Release of WBC’s (neutrophils to bacteria and lymphocytes to virus), which causes
release of cytokins, which allow fluid and macrophages to invade alveoli
Cystic fibrosis – bad Cl- transporter, which allows Na+ to enter, bringing water with it, causing
muco-ciliary elevator malfunction – mucous allowed to dry forming giant “boogers” in lung
Cartilage
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Lacuna – pouch in matrix that chondrocytes make for themselves
Isogenous group – recently divided chondrocytes that temporarily share a lacuna
Matrix composed of territorial matrix (around an individual lacuna, high in GAGs) and
interterritorial matrix (between territorial matrices, low in GAGs)
GAGs of proteoglycans form a gel-like matrix in which proteins are embedded, and through
which water, oxygen, and solutes diffuse
o Aggrecan – negatively charged proteoglycan that attracts water molecules
Hyaline cartilage – type II collagen, multiadhesive proteins, and proteoglycans
Elastic cartilage – hyaline cartilage with elastin in it
Fibrocartilage – hyaline cartilage with type I collagen in it (DCT and hyaline cartilage)
o Chondrocytes in isogenous groups
Perichondrium – collagenous membrane on surface of cartilage
o Carries blood vessels and nerves
o Outer layer – DCT
o Inner chondrogenic layer – mesenchymal cells (source of chondroblasts)
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No perichondrium around fibrocartilage or where cartilage meets bone (as in articular
surfaces)
SOX-9 triggers differentiation from chondroprogenitor mesenchymal cells into chondroblasts
Once a chondroblast is completely surrounded with its own matrix, it is a chondrocyte
Appositional growth – chondroblasts formed by inner layer of perichondrium (cells produce
collagen type I), they produce matrix (collagen type II) and turn to chondrocytes
Interstitial growth – division within lacunae to form isogenous groups
Ollier disease – multiple enchondromas
Maffucci syndrome – Ollier disease with hemangiomas
Bone
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Hydroxyapatite – calcium crystals that form bone matrix
Has collagen and proteoglycans to offer flexibility for durability (hydroxyapatite is for hardness)
Bone serves as storage area for calcium and phosphate
Spongy bone (cancellous) or compact bone (cortical)
Outer layer – periosteum
o Outer layer of this is DCT
o Inner layer has osteoprogenitor cells
Inner layer – endosteum
o Contains osteoprogenitor cells
Red bone marrow – produces various blood cells
o In adults, you only find this in spongy bone (sternum and iliac crest are good places)
Yellow bone marrow – red bone marrow that has been replaced with adipose tissue
Osteoprogenitor cells can be found in Volkmann’s and Haversian canals, as well as periosteum
o Can differentiate into osteoblasts, chondroblasts, adipocytes, and fibroblasts
Osteoblasts – secrete collagen and ground substance (osteoid) – when surrounded by osteoid,
renamed osteocyte – start calcification of matrix by secreting alkaline phosphatase
Death of an osteocyte results in reabsorption of its bone matrix
Osteoclasts – originate from monocytes, live in resorption bays, affected by PTH and calcitonin
(PTH says go and calcitonin says stop)
Lamellae – rings around osteons
Canaliculi – spokes on the wheels of osteons
Haversian canals parallel to long axis of bone
Volkmann’s canals – major route for blood vessels to follow from marrow cavity to periosteum
and from endosteum to Haversian canal
Trabeculae – constantly adjusting to reform body to strengthen against force lines, which is why
lifelong carpenters have larger carpals, etc.
Lack of Vit. D causes lack of Ca which causes soft bones leading to bow-leggedness because of
weight bending femurs – Rickets in kids and osteomalacia in adults
Vitamin A excess can lead to brittle bones
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Vitamin A deficiency results in suppressed endochondral growth
Vitamin C deficiency – scurvy
Skeletal Muscle
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Medial ends of dermomyotome produce Myf5, which forms myoblasts and satellite cells
Lateral ends of dermomyotome produce MyoD, which forms myoblasts and satellite cells as well
Myoblasts give rise to myonuclei, which are located at periphery of muscle fiber within PM
Satellite cells lie outside sarcolemma (PM of muscle fiber) but are enclosed in basal lamina – can
reform the muscles (reconnect muscles) – donate their nuclei to the muscle fiber
Hennemann’s size principle – motor units recruited in order of smallest to largest, so lesser
effort only involves Type I, medium effort involves Type I and IIA, etc.
Neuron releases acetylcholine, which binds to surface of muscle and stimulates calcium cycle,
etc.
Building blocks of a muscle
Sarcomeres form myofibrils which form fibers which form fascicles which form muscles
No myosin heads in the H zone of a sarcomere
Thin filaments – actin, troponin, and tropomyosin
Thick filaments – myosin II
Alpha-actinin – actin-binding protein in Z line – anchors filaments to Z line
Titin – anchors thick filaments to Z line
Nebulin – molecular ruler for thin filament during development
Myomesin and C Protein – found in M line, keeps thick filaments in register
Tropomodulin - actin capping protein that regulates the length of thin filament
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Desmin – intermediate filament protein that surrounds myofibrils/sarcomeres at the level of the
Z-line, keeps myofibrils in register when contracting – UNIQUE TO MUSCLE CELLS
Skeletal Muscle Contraction Cycle
o Acetylcholine causes influx of Na+ which depolarizes sarcolemma.
o Depolarization is conducted deep into fiber by transverse (T) tubules.
o Depolarization activates voltage gated sensors which in turn cause the release of Ca2+
from the terminal cisternae of SR into the sarcoplasm of fiber.
o Calcium binds to Troponin C subunit, causing troponin I to dissociate from actin thereby
exposing the myosin binding site on each actin molecule.
o When depolarization stops due to the breakdown of acetylcholine by
acetylcholinesterase, Ca2+ activated ATPase pumps Ca2+ back into terminal cisternae,
stopping contraction.
o Myosin head is bound to actin in the absence of ATP (Attached Phase)
o Binding of ATP to myosin head reduces the affinity of myosin to actin (Release Phase).
o The energy generated by hydrolysis of ATP into ADP and Pi recocks the myosin head.
(Bending or Cocked Phase)
o Pi is released and myosin head tightly binds to actin, myosin head returns to unbent
position which is a lower energy conformation. This is called the power stroke or force
generation phase.
o ADP is released and the myosin head remains attached to the G-actin in the thin
filament (return to attached phase)
Dystrophin – part of a protein complex that anchors the thin filaments in a muscle fiber to the
sarcolemma and the basal lamina that surrounds each muscle fiber
Gene mutations code for an abnormal protein that causes the sarcolemma to lose its integrity
causing degeneration of the fiber
Duchenne and Becker Muscular Dystrophy – X-linked recessive caused by dystrophin deletions
Myostatin – limits muscle growth – mutations in this cause really buff muscles without working
out
Cardiac Muscle
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Numerous cylindrical cells arranged end to end
sER is organized into single network along sarcomere, extending from Z line to Z line
Macula adherens in vertical part of intercalated discs to prevent them from tearing apart
Gap junction in horizontal part of intercalated discs
Atrial natriuretic peptide (ANP) – hormone produced and secreted by atrial myocytes, increases
excretion of sodium (water follows) from kidney, thereby reducing blood pressure(opposed by
aldosterone)
Smooth Muscle
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Sarcoplasm filled with thin filaments and dotted with thick filaments throughout
Dense bodies – composed of α-actinin attach the contractile apparatus to the sarcolemma
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Contraction of smooth muscles
o Ca2+ binds to calmodulin, and complex binds to myosin light chain kinase, which
phosphorylates myosin
o Myosin is activated to form cross-bridges with actin, and fiber contracts.
o When Ca2+ gets pumped out of cell, phosphatase cleaves phosphate from myosin
inactivating it, and contraction ceases.
Connective Tissue
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Cells that form an ECM – can be resident or wandering (transient)
Fibroblasts – principal cell of connective tissue, synthesize fibers and ground substance
Myofibroblasts – contain actin and myosin, lack a basal lamina, located in LCT
Both fibroblasts and myofibroblasts are involved in wound repair to rebuild connective tissue
Langerhans cells – large aggregates of macrophages
Mast cells – involved in anaphylactic reactions
ECM contains ground substance (proteoglycans, GAGs, and multiadhesive proteins) and fibers
(collagen, reticular fibers, elastic fibers)
Collagen Nomenclature
o [α1(I)]2 α2(I) – type I collagen, made of two α1 chains and one α2 chain
Osteogenesis imperfect – blue sclerae and “glass” bones – caused by type I collagen mutation
Ehlers-Danlos syndrome – mutations of genes of collagen polypeptide chains – causes
superflexibility and can lead to organ rupture
Alport’s syndrome – type IV collagen mutation – hematuria, progressive hearing loss, ocular
lesions
Reticular fibers – type III collagen – form Schwann cells, smooth muscle cells, fibroblasts
Fibrillin – glycoprotein that organizes elastin into fibers
Marfan’s syndrome – mutation in fibrillin gene
Chronic sun exposure – remodeling of fibrillin microfibrils, which leads to nonfunctional elastic
fibers
Most connective tissue formed from mesoderm, but head and face are ectoderm (neural crest
cells)
Wharton’s jelly – mucous connective tissue of umbilical cord
Tendon fibroblasts (tendonocytes) to strengthen and grow tendons as muscles grow
Aponeuroses form sheaths for large muscle groups
Epitendonium – surrounds tendons
Tendons join muscle to bone, and ligaments join bone to bone
Epithelium
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Tissues – basic FUNCTIONAL unit of body (need the whole tissue, not individual cells, to
accomplish stuff)
Characteristics of epithelium
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o Attached to basement membrane
o Has polarity
o Have cell junctions
Epithelioid tissue – in many endocrine glands – like epithelium but lack free surface
Epithelial metaplasia – changing from one type to another (i.e., columnar to squamous)
Microvilli – core of actin filaments bound to plasma membrane by myosin I
o Anchored by a terminal web
o Capped by villin
o Passive movement
Sterocilia – only in epididymis and hair cells of inner ear
o Anchored to plasma membrane by ezrin
o No villin
o Cytoplasmic bridges interconnect adjacent stereocilia
Motile cilia – 9 microtubule doublets connected by dynein “arms” and nexin – 2 central
microtubules
o Basal body – functions as MTOC – alar sheets, basal foot, and striated rootlets hold it in
place
o Effective stroke courtesy dynein and recovery stroke courtesy nexin
Primary cilia (monocilia) – 9+0 axoneme – function as sensors
Nodal cilia – 9+0 axoneme – in bilaminar disc of embryo – rotate counterclockwise to create
current for asymmetric body parts
Ciliogenesis – procentrioles give rise to centrioles which give rise to basal bodies
occluding junctions
o occludins – hills of the Ziploc
o claudins – valleys of the Ziploc
o Diseases like cholera happen when occluding junctions break to allow things through
Anchoring junctions – zonula adherens (interact with meshwork of actin filaments) and macula
adherens (desmosome – interacts with intermediate filaments)
o Formed by cell adhesion molecules (cadherins, integrins, selectins, immunoglobulin
superfamily)
Communication junctions – can pass things between adjacent cells through connexon channels
Basal lamina = lamina densa
o Collagens (type VII and IV), laminins, entactin/nidogen, proteoglycans
o Attached to underlying CT by anchoring fibrils (type VII collagen), fibrillin microfibrils,
and projections of lamina densa
Dystrophic epidermolysis bullosa – mutation in type VII collagen gene – boils and icky skin
Focal adhesions – anchor actin filaments of cytoskeleton into the ECM – stress fibers, function in
cell migration
Hemidesmosomes – anchor intermediate filament of cytoskeleton to the BM
Types of endocrine secretion
o Merocrine – spew particles out
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Apocrine – send out particles in vesicles
Holocrine – explode and send particles out in vesicles
Nerve Tissue
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Neurons start as apolar, then become bipolar as it matures, then differentiates into bipolar or
multipolar or whatever it’s going to be
o Bipolar – interneurons
o Multipolar – motor neurons
o Pseudounipolar – sensory neurons
AP starts at axon hillock
Axosomatic (axon to cell body), axoaxonic (axon to axon), or axodendritic (axon to dendrite)
Synaptic reaction
o Action potential reaches terminal
o Voltage gated calcium channels open
o Calcium binds to proteins on vesicles permitting fusion with terminal membrane
Anterograde – kinesin – proper direction, can be fast or slow, neurotransmitters synthesized in
soma
Retrograde – dynein – opposite direction, can only be fast
Bodies of sensory neurons in DRG
Purkinje cells – roundish body with extensive arborization, only found in cerebellum – sole
output of all motor coordination in cerebellum
Astrocytes – provide structural support in CNS and supervise water and metabolite homeostasis
Satellite cells – astrocytes of PNS
Microglia – immune protection in CNS, engulfs pathogens and presents them to T cells, can kill
bacteria and viruses by throwing H2O2 at them, but this could kill surrounding brain tissue too
Ependyma – synthesizes CSF, cilia on apical surface to circulate CSF, microvilli on apical surface
CSF absorption
o Choroid plexus – modified ependymal cells and associated capillaries in system of brain
ventricles that produce CSF
Oligodendrocytes – CNS myelination – can myelinate many axons at once
Schwann cells – PNS myelination – one cell = one axon because it wraps itself around it
Not myelinated axons
o Group A δ sensory afferents (Pain transmission) = Rapid sharp pain (1st pain)
o Group C sensory afferents (Pain transmission) = Dull throbbing pain
Clefts of Schmidt-Lanterman – myelin imperfections only in PNS caused by areas of Schwann cell
cytoplasm as it wraps around axon
Multiple Sclerosis – autoimmune destruction of myelin
Guillain-Barré syndrome – PNS demyelinating disease, macrophages eat Schwann cells/myelin
Alzheimer’s Disease – proteinaceous plaques and neurofibrillary tangles that accumulate in
brain
Parkinson’s disease – loss of substantia nigra dopaminergic neurons
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Amyotropic lateral sclerosis – characterized by rapidly progressive weakness, muscle atrophy
and fasciculations, muscle spasticity, difficulty speaking , swallowing, and decline in breathing
o Sensory neurons remain intact and no mental decline – only motor problems
o Stephen Hawking is rare survivor of this