SOMA HISTO REVIEWNicole Baumgartner & Kris Nathan

Disclaimer!• This presentation is NOT meant to replace studying from

the power points given for lectures and your reading material!!

• This power point is NOT all-inclusive meaning that what is presented here is high(er)-yield and material that we remember being important / tested on… but this isn’t everything

Cell Cytoplasm & Cell Nucleus• Hematoxylin is not a true basic dye because it uses linker

molecules• Masson’s trichrome is composed of Iron-hematoxylin, Acid

Fuchsin, and Aniline Blue/Green; stains nuclei black, cyotplasm, keratin and muscle fibers red, and collagen and mucus blue/green

• 1 angstrom= 0.1 nm, 10 angstroms = 1nm• Dyneins move to the negative ends of mct, kinesins move to the

positive ends of mct• Mallory bodies and accumulations of keratin are seen in alcoholic

liver cirrhosis • Kartagener’s syndrome: caused by a mutation in dynein motor;

results in sterility, chronic sinusitis, and situs inversus• Know the types of glycogen storage diseases!

Nucleus and Cell Cycle• Knowing apoptosis versus

necrosis• Cell lysis leads to intense

inflammation, accidental death = necrosis

• Programmed cell death, phagocytosis clears up debris = apoptosis

• Stages of the cell cycle and check points

Epithelium• Structure and function: ex- GI secretions are columnar cells• Reversible conversion of one mature epithelial cell type to another cell type,

usually an adaptive response• most commonly columnar to squamous, seen in lungs of smokers• Squamous to columnar seen in lower Barrett’s Esophagus

• Microvilli• Apical domain• Internal core of actin filaments• Core of actin bound to myosin 1 in plasma membrane• Capped by villin• Passive movement

• Stereocilia• Apical domain• Immotile microvilli• Epididymis and hair cells of inner ear• Anchored to plasma membrane by ezrin• No villin• Cytoplasmic bridges interconnect adjacent steocilia

Epithelium Cont.• Motile cilia: axoneme with 9+2 pattern; 9 mct doublets connected by

Dynein arms and Nexin• Associated structures include alar sheet, basal foot, and striated rootlets

• Primary ciliary dyskinesia associated with Kartagener’s syndrome, young’s sydrome

• Lateral domains have CAMs and terminal bars• 3 major groups of occluding junctions: occludins, claudins, and JAMs

• Separates / regulates transport between intercellular and intracellular spaces, limits movement of structures within PM

• 2 types of anchoring junctions: zonula adherens, macula adherins• Communication junctions aka gap junctions- transmembrane channels,

study with injection of dyes into cells or with electrical conductance• Transmembrane channels formed by connexons; open and close with

conformational changes in individual connexons

Epithelium Cont.• The lamida lucida is an artifact of fixation• Basal lamina composed of reticular fibers (type III collagen)

• Attaches to connective tissue through• Anchoring fibrils- type IV collagen• Fibrillin microfibrils• Projections of the lamina densa

• Marfan’s syndrome- mutation in fibrillin, rupture of wall of aorta• Dystrophic epidemolysis bullosa- type VII collagen mutation• Cell to ECM junctions

• Anchoring junctions:• Focal adhesions: anchor actin fillaments of cytoskeleton into the ECM• Hemidesmosomes: anchor intermediate filament of cytoskeleton to the

basement membrane

• Merocrine vs. apocrine vs. halocrine

Connective Tissue• Know difference between resient and transient types of CT

• Ex- lymphocytes? Wandering Adipocytes? Resident• Plasma cells:

• derived from B cells and produce 1 specific antibody• Nucleus displays cartwheel / clock face pattern

• Collagen is the most abundant type of CT fiber (68nm banding pattern)• Collagen types [α1 (I)]2 α2(I) and [α1 (II)]3 are heterotrimeric and homotrimeric

respectively• Osteogenesis imperfecta:

• Type I collagen• Blue sclera / hearing loss• “glass bone disease”

• Ehlers-Danlos syndrome• Mutation in type III collagen• Hyperflex joints, hyperextend skin, vascular and organ rupture

• Alport’s syndrome• Type IV collagen• Hematuria, progressive hearing loss, ocular lesions

Connective Tissue Cont.• Mucous connective tissue

• Found in umbilical cord: “Wharton’s Jelly”• Fibroblasts and few mesenchymal cells

• Loose CT• Sites of inflammatory and immune reactions, most cells are of

wandering / transient type• Dense Irregular connective tissue

• Mostly collagen fibers oriented in various directions• Little ground substance and sparse cells (fibroblasts)• strength and stress resistance

Muscle• Hennemann’s size principle: motor units recruited in order of smallest to

largest [ I IIA IIB]• Know the different layers of muscle: ex: a fascicle is a group of muscle fibers

surrounded by loose CT layer• Thin filament: actin plus tropomyosin and troponin; acts as switch for

contraction• Know which areas of muscle shorten with muscle contraction: I and H ↓• Alpha-actinin: actin binding protein found in Z line, anchors thin filaments to

Z line• Titin: anchors thick filaments to Z line• Desmin: intermediate filament protein that surrounds myofibrils / sarcomeres

at the level of the Z line• Conduction system: Ach causes influx of sodium which depolarizes

sarcolemma, conducted deep into fiber by T tubules, depolarization activates volatge gated sensors which cause release of calcium from the terminal cisternae

Muscle Cont.• The energy generated by hydrolysis of ATP into ADP and

Pi recocks the myosin head (bending or cocked phase)• Dystrophin: anchors the thin filaments in a muscle fiber to

the sarcolemma and the basal lamina• Deletions cause Duchenne and Becker Muscular Dystrophy• Gower’s sign: use arms to get up

• Conduction system of the heart is all muscle cells, not nerve cells

• Dense bodies: contractile elements composed of Alpha-actinin that attach the contractile apparatus to the sarcolemma

Cartilage and Bone• Cartilage is avascular= very limited/no healing• Know the different molecular “recipes” that give rise to each type of

cartilage• Ex: hyaline cartilage characterized by tyoe II collagen gibers, proteoglycans and

multiadhesive glycoproteins• Hylaine cartilage is involved in degenerative diseases such as

osteoarthritis, known to break down as we age• When the perichondrium is NOT present: around fibrocartilage and

when the cartilage contacts with bone such as articular surfaces• Elastic cartilage does not stain with H + E, stains with resorcin-fuchsin

or crcein, does not calcify with aging• SOX-9 triggers differentiation of chondroprogenitor mesenchymal cells

into chondroblasts• When the chondroblast becomes totally surrounded by matrix it then

becomes known as chondrocyte

Cartilage• Bone matrix made of hydroxyapatite• Blood calcium levels are regulated by PTH which raises blood calcium but

stimulating bone resorption (increases osteoclast activity) and calcitonin which reduces blood calcium by suppressing bone resorption and increasing osteoid calcification (decreases osteoclast activity)

• Where do you find spongy vs. compact bone• Epiphysis and metaphysis= spongy• Diaphysis= compact

• In adults: red marrow restricted to areas of spongy bone, especially in sternum and illiac crest

• Death in osteocyte results in bone resorption• Know the stages of endochondral ossification!!• Know the layers of the growth plate!!• Rickets and Osteomalacia: defective matrix mineralization• Vitamin A excess can lead to brittle bones• Osteosarcoma: will see Codman’s triangle

Nerve Tissue• Axon hillock kicks off action potential: sends message• Know chemical vs. electrical synapses (gap junctions direct cell-to-cell

communications)• Neuronal communication requires voltage gated Calcium channels to

open• Fast neuronal transport mediated by kinesin bound to mct, carries large

structures• Bodies of sensory neurons located in DRG and are NOT found in spinal

cord, sensory neurons are pseudounipolar• Motor neurons are multipolar and cell body is in ventral horn• Know the functions of the different types of glial cells

• Ex:Astrocytes regulat K+ concentration of CNS and uptake of glutamate• Satellite cells have been implicated in the persistence of chronic pain• Clefts of Schmidt-Lanterman from cytoplasm displacement as Schwann

cell wraps around an axon

Nerve Tissue Cont.• Neurodegenerative diseases characterized by loss of

substantia nigra dopaminergic neurons• ALS characterized by progressive weakness, muscle

atrophy and fasiculations; death of upper and lower motor neurons in the motor cortex, brain stem, and SC

Blood• 99% RBC, 1% WBC (which cell types does each of these include?)• Serum vs. plasma- wha’ts the difference? Serum has no clotting

factors• Type of hemoglobin prevalent in adults: alpha2beta2• Sickle cell anemia: pont mutation in gene encoding beta globin

chain: valine for glutamic acid at position 6• Most common leukocyte, most numerous in initial response to

infection: neutrophil• Selectin on neutrophil mediate loose binding to endothelium and

allow for “rolling” and transmigration• Has a lobed nucleus which is obscured by stained granules,

involved in hypersensitivity and anaphylaxis = basophil• NK cells are mediators of innate immunity

Blood Cont.• Largest WBC in a smear will be monocytes/macrophages, with

weakly basophilic cytoplasm• Reticulocytes are immature RBC, increased when large

numbers of erythrocytes enter blood stream (ex: blood loss)• Immature neutrophils are band neutrophils• T-cells originate in the bone marrow and mature in the thymus• CD4+ recognize MHC class II, CD8+ recogize MHC class I• Pathogens that are carried to the lymph nodes enter via afferent

lymphatic vessels• MALT is found within the lamina propria• Follicular dendritic cells are not APCs (no MHC II): bind antigen-

antibody complexes via Fc receptors on surface for B cell activation

Blood Cont.• High Endothelial Venules function to concentrate lymph by

transporting fluid and electrolytes from afferent vessels to blood stream

• Thymus (where T cells mature) is mostly replaced by adipose tissue at puberty but can be restimulated under conditions that demand rapid T-cell proliferation, trabeculae form lobules and each has an outer cortex and lighter medulla

• Thymus barrier prevents lymphocytes from encountering antigens

• The spleen is the largest lymphatic organ, collects antigen from the blood

Respiratory System• Nasal cavities:

• Lateral wall contains fold known as nasal conchae or nasal turbinates• Allows for better conditioning of the air• Lined with respiratory epithelium

• Brush cells have small microvilli which likely serve as sensory receptors with afferent nerve fibers found on their basal surfaces…indicate air quality

• Basal cells are short rounded cells that sit on the BM and can undergo mitosis to give rise to other cell types as needed

• Bowman’s olfactory glands are branched tubuloalveolar serous glands, provides medium to dissolve odorants

• Ventricular folds (aka false vocal cords) are lined with ciliated pseudostratified squamous epithelium and have serous glands in lamina propria

• Vocal folds (aka true vocal cords) lined with stratified squamous epithelium and contain a vocal ligament and skeletal muscle

• Wall of trachea has 4 layers: “My Son Can Act” (mucosa, submucosa, cartilagenous layer, adventitia)

• The adventitia is the connective tissue that binds trachea to surrounding structures

Respiratory Cont.• Bronchus has one additional layer, layer 2 = muscularis “Man, My Son

Can Act”• Clara cells secrete lipoprotein that prevents luminal adhesion• Ratio of Cilia to Clara cells changes as you move from terminal

bronchiole to alveoli (more clara cells near alveoli, more cilia near terminal bronchiole

• Pores of Khon: allow for more distal alveoli to become aerated- important with obstructive diseases (allows body to compensate)

• Most abundant surfactant protein? Surfactant protein A- modulates immune response to fungi, bacteria and viruses

• Know the mechanisms of patholgy in COPD and Emphysema: which one has less surface area for gas exchange? (Emphysema) and which one has dynamic hyperinflation of the lung? (COPD)

• Smoking causes what change in respiratory epithelium? Stratified non-keratinized squamous epithelium to simple columnar epithelium!!

Cardiovascular• Pericardium is the sac that surrounds the heart

• Mesothelial cells are squamous epithelium responsible for producing lubricating fluid• Heart valves are composed of 3 layers

• Spongiosa is loose CT layer on atrial side of valve, dampens vibrations with closure • Sympathetic:

• Levels T1-T4-6• Norepinephrine• Tachycardia and dilation of coronary arteries

• Parasympathetic• Vagus nerve• Acetylcholine• Bradycardia and constriction of coronary arteries

• Baroreceptors, Volume Receptors, and Chemoreceptors: Know where they are located and what they sense!

• Ex: volume receptors located in walls of atria, provide info about cardiac distention• Know the functions of endothelial cells as it pertains to important role in blood homeostasis• Damage to endothelial cells produces prothrombogenic vonWillebrand factor• NO produced by endothelial cells causes vasodilation, decreasing blood pressure• Endothelin causes influx of Calcium which increases contraction and blood pressure• Arterioles are flow regulators to capillary beds• In hypertension: smooth muscle cells hypertrophy thickening the tunica media• In atherosclerosis: lesions of foamy macrophages deposit in the tunica intima

Digestive System• Know general pattern of increasing # of goblet cells and decreasing # of villi as you move

down the alimentary tract• Amylase and lipase in mouth (from parotid and Von Ebner’s glands respectively) begin

digestion of carbohydrates and lipids in mouth• No digestion takes place in oropharynx and esophagus (neutral mucus)• Esophageal-cardiac junction is an abrupt transition between esophagus and beginning of

stomach; marked by abrupt change from stratified NK squamous to simple columnar (respectively)

• To identify stomach: note that gastric glands do not project beyond the muscularis mucosa • Know which digestive enzymes chief cells secrete• APUD cells secrete off of their basal surfaces• Zollinger-Ellison syndrome caused by a gastrin secreting tumor in duodenum or pancreatic

islet, ulcer forms from excessive HCl secretion• Know the adaptations to increase surface area: 3X = plicae circularis, 10x = villi, 20x=

microvilli (found all over small intestine)• Cells of intercalated ducts secrete bicarb and water, acinar cells secrete digestive enzymes• Absorption of products in digestive tract: peptides, carbs, and small lipids enter blood

supply while long chain FA as chylomicrons enter lymphatic supply called lacteals

Digestive System Cont.• Colon:

• Cypts but NO villi• Large # goblet cells• Outer longitudinal layer of SM modified to form teniae coli

• Chron’s disease• Occurs in any region but usually illeum• Skip lesions => cobblestone appearance• Lower right quadrant pain• String sign

• Ulcerative colitis• Occurs in colon / rectum• Usually restricted to mucosa / submucosa

• Pectinate line in anus demonstrates tissues from 2 different embryonic origins

Accessory Organs of Digestive System• Know the hormone regulators of Exocrine pancreatic secretions! Specifically which cells secrete

them and what are their functions• What are the mechanisms that prevent autodigestion of the pancreas?• Understand the organization of the hepatic lobule • Hepatic stellate cells are vitamin A storing cells that transform into collagen secreting cells after

insult, responsible for liver cirrhosis• In the classic hepatic lobule: drains blood from the portal vein and hepatic artery to the hepatic or

central vein• Also understand the role / function of portal lobule (bile) and portal acinus

• In the portal acinus, which zone will be most injured from toxin in blood and which one will be most injured from lack of blood supply?

• Zone 1 and 3 respectively• Bile canaliculi are not about by epithelium just by hepatocyte cell membrane, tight junctions

prevent bile from leaking out• Gall bladder folds appear as artifactual spaces known as Rokitansky-Aschoff cypts, if these

extend into muscularis mucosa they are pre-pathological• Important in concentration of bile: Sodium/potassium ATPases• Know the different types of gallstones, what each is made of, and what pathological conditions

predispose you to these stones• Know the 3 ways a person can become jaundiced

Urinary System• Know the anatomical structure of the kidney- Things merge to form other parts of the kidney

• Ex: Major calyces form renal pelvis• Renal a. interlobal a. arcuate a. interlobular a. afferent arterioles

• Branching to become arcuate a. happens at the corticomedullary junction (the base)• Nephron= functional unit of the kidney• Bowman’s capsule has 2 layers: visceral and parietal epithelial layers

• Parietal = simple squamous• Visceral= podocytes

• You will only see renal corpuscles in the cortex• Mesangial cells are found within the GBM, play an important role in phagocytosis and endocytosis,

structural support, and distention modulation• Proximal Convoluted Tubule:

• Sodium-potassium ATPase pumps- reabsorption of sodium is driving force for reabsorption of water• Adjusts pH via reabsorption of HCO3- and secretion of organic acids/bases

• Thin ascending loop cells produce uromodulin which is an important influence in NaCl reabsorption and concentrating ability

• Urine flow: urine leaves collection tubules area cribosa, enter minor calyx, drains into major calyx, empties into renal pelvis

• Urothelium, a type of transitional epithelium, lines the passages leading from the kidneys• Ureters made of 3 muscle layers: longtudinal, circular, and longitudinal (outer longitudinal is only present

at distal end)• Uroplakins are responsible for distention capabilities of the bladder (folds of epithelium that can distend)

Endocrine System• Know the difference Endocrine vs. paracrine vs. apocrine• Know 3 classes of hormones and where they are secreted and where they

typically act:• Ex: steroid secreted into blood, transported via plasma proteins, act in nucleus of target

cell• Anterior lobes of pituitary are derivatives of Rathke’s pouch; know the 3 “pars”• Know the table with all of the anterior/posterior pituitary hormones (production

site and function)• Ex: growth hormone from somatotropes stimulates liver and other organs to produce IGF-

1, results in progenitor cell division and body growth• Anterior pituitary histologically identifiable with colloid filled follicles• Know the hormones of the hypothalamus and which cell types they

inhibit/cause release of• Ex: somatostatin inhibits secretion of GH

• Melatonin from pinealocytes is responsible for regulation of circadian rhythms

Endocrine Cont.• Follicular cells produce T3 and T4, Parafolicular cells

produce calcitonin (know the functions of these hormones)• Iodination of thyroglobulin occurs in the colloid• Principal cells of parathyroid produce PTH- know its role in

calcium regulation• Know the layers of the adrenal gland: “Salty-Sweet-Sex”

• Zona glomerulosa: mineralocorticoids, under control of RAA system• Zona fasciculata: glucocorticoids, know their actions at specific tissues• Zona reticularis: weak androgens (mainly DHEA)

• Endocrine Pancreas:• Alpha cells= glucagon• Beta cells= insulin• Delta cells= somatostatin

Male Reproductive• Enclosed in dense CT called the tunica albuginea• Each lobule consist of 1-4 seminiferous tubules surrounded interstitium

• Interstitium houses blood vessels, nerves, lymphatics and Leydig cells• Know the number of cells present at each stage of spermatogenesis and know

haploid vs. diploid• At which stage are spermatids no longer connected?

• Know the key events in spermiogenesis• What allows germ cells to develop in absence of circulating antibodies, Formed by

tight junctions of adjacent Sertoli cells? Blood-testis barrier• Know the role of LH, FSH, and inhibin in spermatogenesis• Sertoli cells:

• Nourish spermatozoa, concentration of testosterone, blood testis barrier

• Interstitial cells of Leydig secrete testosterone essential for spermatogenesis• Ductus epididymis:

• Lining is pseudostratified columnar with stereocilia; function is to absorb testicular fluid• secretes glycerophosphocholine, a glycoprotein- prevents capacitation of spermatozoa

Male Repro Cont.• Seminal vesicles: lined by a pseudostratified columnar epithelium is highly folded into a

labyrinth• Prostate secretes fluid rich in serine proteases (PSA), fibrinolysin, citric acid and

seminalplasmin, serve to liquefy semen• BPH= hypertrophy of glands in transitional zone• Prostatic cancer= malignant growth in peripheral glands• Cowper’s glands: Mucus produced by glands precedes release of semen and may have

a lubricating function• Corpora cavernosa are surrounded by a dense band of connective tissue called the

tunica albuginea• Urethra courses through corpus spongiosum• “Point and Shoot”: parasymp = point, sympathetic = shoot• S 2, 3, 4 keeps your “stuff” up off the floor!

• Sympathetic (L1-2) closure of internal urethral sphincter• Parasympathetic (S2-4) : Contraction of urethral muscles • Spinal reflex (S2-4): Forceful contraction of the ishiocavernosus and bulbocavernosus muscles of the pelvic floor aid in

ejaculation (propulsion of sperm).