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Patho Final Notes - Dr. Goldsmith

Introduction To Human Physiology And Pathophysiology (MCPHS University)

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EXAM 1:

Adaptation: adjust to ∆ in internal envt: atrophy (smaller cells), hypertrophy (larger cells),
hyperplasia (more cells, like calluses), metaplasia (1:1 ∆ in adult cell type), dysplasia (different
cell sizes/shapes/organizations within the same tissue, not 1:1)
Cell injury/death:
Ir/reversible, healthy cell  (insult/injury)  cell injury  death; causes:
-physical agents (force/impact, temp extremes, electrical injury)
-radiation injury (ionizing high-freq radiation  free radicals form, UV radiation  sunburns,
nonionizing radiation/lower freq, ex: IR/ultrasound/microwaves/laser  atomic vib/rot)
-chemical injury (drugs, metals, pollutants), mech: cell damage, enzyme interference, protein
denaturation, disrupt osmotic/ionic balance
-biologic agents (viruses incorporate DNA, bacteria use exo/endotoxins, fungi, parasites)
-nutritional imbalances (deficiencies: vitamins, minerals, protein, carbs, fat, starvation;
excesses: obesity, saturated fat)
Mechanisms of cell injury:
-free radical injury: chemicals w/unpaired outer electron(s), unstable, normal cell rxns  free
radicals (cell resp, møs), extrinsic factors (smoke, radiation), antioxidants protect,
radiation/toxins  oxygen toxicity/inflammation/ischemia  enzymes remove radicals
-hypoxic cell injury: O2 deprivation (low aerobic metabolism/ATP production),
reversible/irreversible depending on degree of deprivation/cell needs
-causes: low O2 (pure hypoxia), resp disease, ischemia (low blood flow), anemia, edema
-mechanism: cell power failure, oxidative metabolism falters  anaerobic  less
energy); lactic acid accumulation  pH falls (chromatin clumping, membrane and
intracellular destruction); E loss  Na/K-ATPase membrane pump  swelling
-impaired Ca homeostasis: cell messenger in ER/mitochondria, intracellular usually low,
extracellular high (maintained by Ca/Mg-ATPase), toxins/ischemia can increase  cell
damage from activated enzymes
Reversible cell injury/death: cellular swelling (impaired Na/K-ATPase from hypoxia), fatty
change (severe injury, vacuoles of fat in cytoplasm, high fat load/low fat metabolism,
liver/heart/kidneys)
Cell death:
-apoptosis (controlled destruction/suicide, normal process; development, maturation, repair;
lack of apoptosis in proliferation of CA cells, hepatocyte death in hep B/C); controlled
autodigestion via endogenous enzymes, shrinkage  cytoskeleton disrupted, organelles
condense, nuclear DNA disrupted/condensed, nucleus breaks into spheres, membrane
wrinkling  cell divides into fragments covered in membrane
-necrosis (unregulated due to injury, swelling/rupturing  inflammation), part of a living
person, enzymatic component digestion, membrane integrity loss, uncontrolled product
release; different types:
-liquefactive necrosis: center of abscess: tissue softening, catalytic enzymes fxnal
-coagulation necrosis: hypoxic injury/infarct: gray/firm mass, acidosis  protein
denaturation
-gaseous necrosis: Tb granulomas: dead cells persist as soft cheeselike debris

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-gangrene: large area of necrotic tissue, dry (lack of blood supply but can carry fluid out
to coagulate tissue) or wet (fluid accumulates in tissue, which liquefies; infection likely); gas
gangrene: clostridium infection  toxins/H2S bubbles
Cell change with aging: telomeres too short, cell can’t divide  programmed; or older cells
have more DNA damage/free radicals and less telomere reparation  result of damage
Acute vs. chronic inflammation: depends on: injury persistence, symptoms, nature of response
Acute: accumulation of fluid/plasma in tissue, intravascular platelet stimulation, PMNs
-short: minutes/days, hallmarks: rubor (red), dolor (pain), calor (heat), tumor (swelling),
function laesa (loss of fxn), denoted by -itis
-outcomes: resolution, abscess, scar, persistence
-vascular (hemodynamic) stage: transient vasoconstriction, rapid arteriole/venule
vasodilation around injured area, increased permeability of vessel endothelial cell barrier
-cellular stage: PMNs then møs
Increased vascular permeability: circulating PMNs and chemotactic factors 
margination/adherence  emigration  chemotactic migration  phagocytosis
Inflammatory mediators: tissue injury like trauma, ischemia, neoplasm, infection, particle 
one of the following:
-vasoactive mediators (histamine, serotonin, bradykinin, anaphylatoxins, leukotrienes-
prostaglandins, platelet activating factor)  increased vascular permeability  edema
-chemotactic factors (c5a, lipoxygenase products like LTB4, formylated products,
lymphokines, monokines)  inflammatory cell recruitment/stimulation  acute
(PMNs/macrophages) or chronic inflammation (møs, lymphocytes, plasma cells)
Vasoactive mediators:
-plasma: complement activation (anaphylatoxins c3a/c5a) and Hageman factor
activation (bradykinin), chemotactic: complement activation c3a/c5a
-cell: mast cell/basophil degranulation (histamine), platelets (serotonin), inflammatory
cells (leukotrienes, prostaglandins, platelet activating factor); chemotactic: cell membrane
phospholipids (lipoxygenase products LBT4), inflammatory cells (chemokines = lymphokines,
monokines), bacterial/mitochondrial (formylated)
Chronic: lymphocytes, plasma cells, møs, fibroblasts (risk of scarring/deformity); long, self-
perpetuating, weeks to years, contains/removes pathologic agent/process
-causes: recurrent/progressive acute inflammation; low-grade persistent irritants that
can’t penetrate deep/spread rapidly;
-nonspecific chronic or granulomatous
Inflammation manifestations: local: swelling, exudates (serous, hemorrhagic, fibrinous,
membranous, purulent/suppurative), abscess, ulceration; systemic: acute-phase response, WBC
count changes, fever
-acute-phase response: leukocytes release interleukins/TNF: affect thermoregulatory
center  fever, affect CNS  lethargy, skeletal muscle breakdown; liver makes fibrinogen/C-
reactive protein: clotting, bind to pathogens, moderate inflammatory response
Tissue repair: regeneration: repair of injured tissue w/cells of same parenchymal type
(parenchymal tissue, stromal tissue, labile cells, stable cells, permanent fixed cells); connective
tissue repair: scar tissue instead of parenchymal cells of injured tissue
Wound healing: depends upon tissue loss extent, occurs via primary/secondary intention

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-phases: inflammatory (just seen), proliferation (granulation tissue

angiogenesis/growth, fibroblast emigration, extracellular matrix deposition), remodeling:
fibrous tissue maturation/reorganization
-factors: malnutrition, blood/O2 delivery, impaired inflammation/IR, infection/wound
separation/foreign bodies, age
Cell differentiation/growth: cell cycle
G1: RNA/prot synth, growth, time varies by tissue (labile, cyclins ensure cell large enough to
divide)
S: DNA synth, 2 csome sets, 10-20h (labile, cyclins ensure DNA duplication)
G2: premitotic, 2-10h (labile, cyclins ensure cell made csome separation proteins)
M: mitosis, 30-60min; cells  permanency, G0, or G1 (labile)
G0: resting, time varies by tissue (stable)
3 different types of cells with respect to differentiation:
-highly differentiated
-progenitor: partially differentiated, replace mature cells of same lineage
-stem: uni/oligo/pluripotent
Tumor: condition leading to swelling (often neoplasm)
Neoplasm: abnormal mass where growth exceeds normal tissues
Benign (from differentiated working cells): well-differentiated, progressive/slow, may
stop/regress, expands w/o invasion, encapsulated, single mass, usually no death
Malignant (from undifferentiated rapidly dividing cells): less well-differentiated, varies
in growth, invasive (sends out processes) can break loose (metastasize), death if untreated
-oma: suffix to parenchymal tissue type for tumor name
Cancer cell characteristics: no normal cell proliferation/differentiation; from mutations in
differentiation, early in process: less differentiated/more malignant; late in process: more
differentiated, less malignant; grading based upon differentiation degree, proliferating #cell;
loss of contact inhibition/cohesiveness/adhesion/cell-cell communication, expression of altered
tissue Ags, production of degradative enzymes for invasion/metastasis
Tissue invasion/metastasis: seeding (entering body cavity), metastasis: leave 1° tumor, invade
ECM, enter/survive blood/lymph, growth location, invade tissue/grow
Tumor growth: depends on #cells dividing/being lost vs #produced, cell cycle duration; tumor
growth due to increased #dividing cells (don’t’ die on schedule, lack growth factors for G0
phase; blood supply/nutrients limit growth
Oncogenesis: normal cells  cancer cells, proto-oncogenes: growth-stimulating regulatory
genes (encode growth factors/2nd messengers); tumor suppressor genes/anti-oncogenes:
growth inhibiting regulatory genes; genes controlling apoptosis; DNA repair genes
Cancer cell transformation: multi-step process: initiation  promotion  progression
Risk factors: interactions among multiple are necessary: hereditary, hormones, obesity,
chemical carcinogens, radiation, viruses, immune dysfunction
Clinical manifestations: organ function ∆ (damage/inflammation/failure), local effects
(nerve/vein compression, GI obstruction); tissue integrity (nonspecific signs like protein/bone
breakdown); paraneoplastic syndrome (ectopic hormones from tumor cells); cancer cachexia
(weight loss, muscle wasting, weakness, anorexia, anemia)

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Treatment: surgery, radiation, chemotherapy, hormonal, biotherapy (immunotherapy, biologic

response modifiers), targeted, transplantation)
Chemotherapies: cell cycle specific S phase inhibitor (MTX), microtubule structure disrupters
(taxanes/vinca alkaloids), DNA-topoisomerase inhibitors

EXAM 2:

Fxns of cell membrane: homeostasis/cell survival (mechanical barrier, adhere to form tissues,
exchange nutrients/waste/secretion, respond to ∆, maintain ionic gradient)
Components: lipids (phospholipids/cholesterol): barrier to passage of water soluble substances,
fluidity for membrane; proteins (transmembrane or one surface only): several types/fxns (ion
channels, carriers, receptors, enzymes, cell-adhesion molecules CAMs); carbohydrates (outer
surface only): glycolipids, glycoproteins, self-ID markers
Cell-cell adhesions: cells tissues organs system organism, extracellular matrix = biological glue
from cells, cell adhesion molecules (nearby cells, loop/hook like Velcro), specialized cell
junctions (desmosomes, tight jxns, gap jxns)
Extracellular matrix: interstitial fluid, meshwork of fibrous proteins in watery gel (complex
carbs): collagen/elastin/fibronectin; amount/composition varies w/cell type, pathway for water
soluble substance diffusion, regulates behavior/fxns of cells (cartilage/tendons/hardness of
bones/teeth)
Desmosomes/adhering jxns: spot rivets, plaque, glycoprotein filaments, keratin filaments, in
skin/heart/uterus
Tight/impermeable jxns: cells adhere firmly, jxnal proteins, found between epithelial cells,
separate 2 diverse compartments (intestines/kidneys), passage through cells via
channels/carriers
Gap/communicating jxns: gaps/tunnels between cells, connexons: 6 subunits in a tube, 2 join
together; only small particles pass, electrically active cardiac/smooth muscle, synchronized
action, metabolic/communication link
Membrane transport: essential for homeostasis, lipid solubility/particle size affect
permeability: high lipid solubility, low lipid but <0.8nm diameter, low lipid but >0.8nm
diameter; forces required (passive: no E spent, active: E spent)
Diffusion: high to low conc, only if substances can cross, no E required  passive like O2/CO2,
Fick’s law of diffusion (high conc gradient/surface area/lipid solubility and low MW/thickness 
higher diffusion rate)
Electrical gradient: charge difference between adjacent areas, promotes movement toward
opposite charge, electrical + conc = electrochemical gradient
Osmosis: net H2O diffusion down its conc gradient separated by semipermeable membrane,
tonicity: conc of non-penetrating solutes, determines if water moves in/out; isotonic: same
tonicity for IV admin/eye drops, hypotonic: less/below, hypertonic: more/above
Carrier-mediated transport: utilize carriers (membrane spanning proteins), can flip-flop
(reverse change in shape), binding site exposed alternatively to either membrane side;
specificity/selectivity: one carrier one substance or closely related, different cells  different
carriers; saturation: finite #carriers, rate-limiting factor, affinity/# regulated (insulin), T m =

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transport max, transport proportional to conc under Tm, competition: carrier transfers closely
related substances, diminishes rate but not amount
Facilitated diffusion: high to low conc substance movement, no E needed
Active transport: low to high conc (iodine uptake by thyroid), needs E/ATP like H pumps or Na/
K/ATPase pumps (Na outside, K inside sequentially, regulates electrical signals and cell volume
via tonicity), primary (ATP directly needed), secondary (ATP not directly needed)
Secondary active transport: glucose/amino acid co-transport, intestinal/kidney cells, E
mediated by co-transport carriers, 2 binding sites (one for Na another for nutrient), Na binding
increases affinity for glu binding, transported by facilitated diffusion

EXAM 3:

Vesicular transport: large/polar (hormones/bacteria), active transport, don’t mix with

cytoplasm, may fuse with target organelle like lysosome, can secrete on the other side of cell
Endocytosis: into cell
Pinocytosis: ECF, non-selective
Phagocytosis: engulfs bacteria to prevent infection
Receptor-mediated: tolerance opioids bind to receptor, which moves into cell
Exocytosis: out of cell
Hormones: secreted inside vesicle in cell and released into ECF, ion channels
Communication:
Direct: Juxtacrine: two cells with transport junctions (gap junctions/connexons),
Indirect: majority, chemical messengers (NTs, hormones), may not cross membrane
Paracrine (histamine): local, doesn’t reach circulation
Autocrine: local, doesn’t reach circulation, auto = self
Endocrine (hormone): travel far to receptors on target cells
Neuronal: electrical signals to glands/muscle, small gap  neurotransmitters
Neurohormone: Adrenal medulla  blood, nerve sends epinephrine
Substances that can’t get into the cell  receptors/transducers transduce the signal
Ions, 2nd messengers
Ion channels:
Leak (no drug targets): always open, electro/chemical gradient
Gated (drug targets):
Ligand: acetylcholine, Na influx  signal
Voltage: membrane potential, ion in/efflux  signal
Receptor proteins yield 2nd messengers (cAMP/Ca), which activate other proteins, etc 
signaling cascade
Membrane potential: membrane has the potential to do work, measured in millivolts (charges
move to equalize across membrane, releasing energy)
resting membrane potential RMP = -70 mV, depolarization: first half of peak (less negative),
repolarization: second half of peak (more negative again), hyperpolarization: more negative still
Na/K ATPase: 3Na out 2K in
Nernst eq for potassium in mV: EK = 61*log(Co/Ci)

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Brain/spinal cord: central, everything else is peripheral; input to CNS by afferent

(sensory/visceral stimuli), output from CNS by efferent (somatic w/motor neurons, autonomic
with para/sympathetic NS)
Cell body w/nucleus/organelles, axon hillock (action potential trigger zone with voltage Na
channels) connects body to axon/nerve fiber (one long tube, maybe myelin sheath, signals
from body), dendrites (input, more SA, signals to body, receptors for NTs, graded potential
initiation), axon terminals (output zone, release NTs)
CNS: interneurons from afferent to efferent, ANS axon terminals, ENS cell body/dendrites
Input zone between ANS axon terminals and interneuron cell body, initiates graded potentials
Depolarization (excitatory) at 55 mV  Na influx, depolarization; hyperpolarization (inhibitory):
K efflux Cl influx
NT opens Na channels to let Na through
Graded potential: short distances, magnitude/duration proportional to that of triggering event,
spread by passive current flow in all directions, spatial summation and temporal summation
Photo light, mechano BP, thermo temp, noci pain, osmo osmotic pressure, chemo chemicals
(nose/tongue)
Action potential: RMP -70, threshold -55  depolarization (increase of 100), back down 
hyperpolarization  repolarization; sodium (activation and inactivation gates, rapid A opening
and slow I closing triggered at threshold) and potassium (delayed opening triggered at
threshold) channels both voltage-gated
Reach -55 (depolarization, A gate of Na opens)  peak at 30 (I gate of Na closes and K gate
opens)  back down to -70 again (repolarization, A gate open and I gate close)  past -70
(hyperpolarization)  back to -70 again (K gate closes)  Na/K ATPase restores balance
Action potential characteristics: all or none, speed depends on nerve fiber diameter,
conducted through axon once initiated, touch conduction in unmyelinated neurons, ONE WAY,
backward flow doesn’t re-excite because area is in refractory period, forward current flow
excites new area
Absolute refractory: no AP, Na channels closed and not capable of opening, relative: stronger
stimulus can generate AP, until potential returns to -70
Nerve fiber types:
A myelinated, cutaneous pressure/touch/cold, mech/heat pain, 3 types (fastest)
B myelinated, sub/cutaneous mechano
C unmyelinated, warm-hot, mechanical/chemical/heat-cold pain (slowest)
Myelin sheath made of lipids, poor conductor so potential jumps to Nodes of Ranvier (which
has 2Na 2K channels across from one another (saltatory  faster conduction, conserves E)
Multiple sclerosis: myelin sheath damage, slow/block AP propagation
Synapses: AP reaches pre terminal, Ca open and Ca enters synaptic knob (pre terminal), NT
released by exocytosis, NT binds to ion channels, LGICs open, GPs sum  Aps, NT removed fast
Types of synapses: excitatory  Na influx / EPSP closer to -50 from -70 (more positive);
inhibitory: Cl/K influx / IPSP farther from -50 from -70 (more negative)
Neurotransmitter: small molecule AA, act/destroyed quickly, local synthesis, synaptic vesicle
storage, open LGICs or use 2nd messenger systems in post neuron, make EPSP/IPSP
Neuropeptides: large molecules 2-40 AAs, act slowly, prolonged response, cell body synthesis,
dense core vesicle storage, 2nd messengers pre/post, no EPSP/IPSP

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Tonic: don’t adapt, or adapt slowly, maintained info about stimulus is variable
Phasic: adapts rapidly but generates an off response, change in intensity important
CNS components: brain/spinal cord: axon terminals of afferent, interneuron (100 billion), cell
body of efferent
Glial cells: no signals, provide physical/metabolic/functional support, viability/90% of CNS,
unchecked division causes brain tumors
Astrocytes: star, supports/guides neurons, blood brain barrier, brain injury repair, take
up NT, take up K during high frequency Aps, forms synapses via thrombospondin
Microglia: immune defenders/scavengers, secrete NGF
Ependymal cells: form/flow cerebrospinal fluid, neural stem cells
Oligodendrocytes: CNS myelin sheath
CNS protection: bone: protective hard shell (cranium for brain, vertebral column for spine),
CSF: shock absorber (choroid plexus with cilia), wastes and unnecessary solutes absorbed,
blood-brain barrier has tight junctions (lipid-soluble substances, astrocyte processes, carrier-
mediated transport)
Mater membranes: protective/nourishing, blood brain barrier
Dura/subdural space/arachnoid mater/subarachoid space/pia mater
Dura: tough/inelastic/outer
Arachnoid: vascularized, middle
Pia: vascularized, adhering, inner
Cerebral cortex, longitudinal tissue between, thin gray matter on outside (dendrites, cell bodies,
glial cells), thick white on inside (myelinated axons), corpus callosum between, left motor
cortex controls right side of brain
Frontal: voluntary motor, speaking (left), higher order; parietal: receiving/processing sensory
input, language comprehension, parietal temporal occipital AC: integration of somatic, visual,
auditory sensations from 3 lobes, occipital: initial visual input processing, temporal: all sensory
input integration, AC: motivation, emotion, memory, prefrontal association cortex: planning
voluntary activity, decisions, personality, creativity
Primary motor cortex: voluntary motor activity in front of central sulcus, temporal lobe
Somatosensory cortex: parietal lobe, behind central sulcus, processes sensory activity, intense
spatial discrimination
Language: primary motor cortex, Broca’s area (left hemisphere, programs sound pattern of
speech), primary auditory cortex, Wernicke’s area (plans content of spoken words), parietal
temporal occipital AC (integrates sensory input), primary visual cortex (perceives sight)
Primary visual/auditory cortexes  PTO association cortex  Wernicke  broca  primary
motor cortex
Basal nuclei/ganglia: white matter, caudate nucelus/putamen/globus pallidus/claustrum,
promotes purposeful muscle, inhibits useless movement/muscle tone (tremors),
slow/sustained contractions, doesn’t work well in Parkinson’s
Nuclei: neuronal cell bodies inside cell system, ganglia: neuronal cell bodies outside system
Thalamus: relay/integration for sensory input to cerebral cortex, screens out insignificant
signals, routes important signals to cerebral cortex, directs crude sensation awareness
(warm/hot, location intense), consciousness

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Hypothalamus: homeostatic fxns, nervous/endocrine link, sleep-wake cycle, circadian rhythm,

limbic system (2nd order to 3rd order)
Limbic system: ring of forebrain around brain stem, reward/punishment (drugs of abuse)
w/NE/DA/5-HT neurotransmitters, cortex: (emotions/survival/motivation/learning/socio-sexual
behavior); psychiatric (depression/psychosis), fear (amygdala), smileblind
Cerebellum: promotes muscle tone, balance, skilled movement, voluntary activity, procedural
memories, eye movements
Brain stem: spinal cord, life sustaining processes (respiration, circulation, digestion, excretion),
activity/movement of head/neck organs, reticular activating system sends out into outer brain,
sleep centers, consciousness, midbrain/pons/medulla
Spinal cord: 45cm long 2cm diameter; nodes: cervical, thoracic, lumbar, sacral, coccygeal 31
pairs, vertebrae longer than spinal cord, cauda equina: tail horse, lumbar/sacral (spinal taps for
meningitis, and local anesthetics for labor)
PNS: sensory receptor  afferent neuron  cell body )dorsal root afferent, ventral root
efferent), a nerve contains afferent/efferent neuron, mostly interneurons in brain so few nodes
White matter: ascending nerve on dorsal and sides, descending nerve on ventral, axons
Afferent: myelinated axons, ascending from body to brain
Efferent: from brain to body
Gray matter:
dorsal (cell bodies of interneurons where afferent neurons end), lateral (cell bodies of
autonomic efferent nerve fibers), ventral horn (cell bodies of somatic efferent neurons), link
between brain/body, integrates reflex w/o brain; dendrites/cell bodies/glial cells
Reflex arc: thermal pain receptor in finger, afferent pathway, integrating center (spinal cord),
efferent pathways, effectors, and finally ascending to brain
Components: receptor, afferent pathway, integrating center, efferent pathway, effector

FINAL EXAM:

4/10

Efferent PNS: communication link, CNS controls effector organ activity

Autonomic NS: involuntary (cardiac/smooth muscles), exocrine/some endocrine
Sympathetic/parasympathetic NS
Somatic NS: voluntary/skeletal muscles
Allows CNS to control muscles/glands/secretions/movement  homeostasis
Autonomic nervous system: pre/postganglionic fibers with autonomic ganglion between,
releases two different NTs on structure it controls, acetylcholine/norepinephrine
CNS  preganglionic fiber  preganglionic NT through autonomic ganglion 
postganglionic fiber  varicosity  postganglionic NT to effector organ (smooth/cardiac
muscle)
Sympathetic: nerves from thoracic/lumbar, pre fibers short/release ACH, post
long/release norepinephrine (adrenergic), synapse within sympathetic ganglion chain/collateral
ganglion

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Parasympathetic: nerves from cranial/sacral CNS, pre fibers long/release ACH, post
fibers short/release ACH (cholinergic), most synapse at terminal ganglia near effector organs
Control of ANS: involuntary visceral organ responses, receive dual innervation by both ANS
subdivisions to control internal organ activity, opposite effects, predominate at given moments
Sympathetic dominance: prepare for emergency/stress fight/flight/fright, increases
oxygenated/nutrient-rich blood to skeletal muscles for physical activity
Dilates skeletal blood vessels
Higher heart/resp rate
Glycogen  glucose in liver
Sweating
Dilates pupils/bronchioles
Less digestion/urination
Parasympathetic dominance: quiet/relaxed situations, housekeeping, conserve E
Lower heart/resp rate
More digestion/urination
Dual/reciprocal innervation: allows precise control over effector organ activity, except:
arterioles/veins/sweat glands sympathetic, salivary glands both systems lead to salivation
(para  watery, symp  mucus)
Target specificity: multiple receptors from NE and ACH at different locations/coupled to
different pathways, different kinds may have different sensitivity
Somatic NS: skeletal muscle via motor neurons, axons constitute SNS, cell bodies lie in ventral
horn; different from ANS: axons do not synapse in ganglion, can only stimulate skeletal
contraction; diseases: polio (cell bodies paralyzed), Gehrig (ALS) (motor neurons degenerate)
Horns: cell bodies, dorsal: afferent neurons terminate on interneuron, lateral: autonomic
efferent, ventral: somatic efferent

4/13

Neuromuscular junction: efferent myelinated, terminal branches unmyelinated  NMJ,

terminal button: terminal at muscle fiber, voltage gated Ca channel lets it into ACH vesicle, NT
released by exocytosis when action potential reaches terminal button  end plate potential
motor end plate: muscle cell membrane below TB, ACH-gated receptor channel: on motor
endplate, allows nonspecific cation traffic (more likely Na in, less likely K out  small gated
potential, membrane closer to -70 threshold; when it hits, Na channels around motor end plate
will activate and Na will go into cell  action potential across muscle fiber), enzymes like
acetylcholinesterase break down ACH so this potential stops, junction vulnerable to chemicals/
diseases:
Toxins: black widow venom (release ACH), botulinum (can’t release ACH)
Curare: blocks receptors at motor end plate
Organophosphates: irreversible acetylcholinesterase inhibitors
Myasthenia gravis: lose ACH receptors at MEP, autoimmune disease, muscle weakness

Muscle physiology
50% body weight, contract for movement

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Skeletal: 32% women 40% men BW, striated, voluntary

Cardiac: striated, involuntary
Smooth: unstriated, involuntary
Muscle cell = large/elongated/cylindrical along entire muscle, multiple nuclei/mitochondria
(from myoblasts that fuse  myotubes, myosatellite cells help w/muscle repair/regeneration),
tendons connect to bone, epimysium around whole muscle, perimysium in between
endomysium, muscle fiber is a single cell inside an endomysium, each fiber contains multiple
nuclei and mitochondria
Structure: contractile myofibrils make up length of muscle fibers, 80% of fiber volume, regular
arrangements of thick long (myosin) and thin short (actin)
Sarcomere: functional unit of myofibril, A band: myosin stacked with actin, dark zone, H zone:
myosin without actin, M line: vertically down center of A band/sarcomere connecting myosin to
each other for support, I band: section of actin outside A band, sarcomere shortens when
calcium is released
Thick filament: several hundred myosin, myosin: two identical subunits, golf club, heads form
cross bridges, tails intertwined toward center, each head has an actin binding site and a myosin
ATPase site (ATP  E), cross bridges: seen electron microscope (thick to thin), attach to actin
Thin filament: G-actin globular with site for myosin cross-bridge, F-actin filament (helix)  add
tropomyosin thread/troponin (bind to tropomyosin/actin/calcium) to get thin filament
Thick/thin = contractile proteins, troponin/tropomyosin = regulatory proteins

4/15

Relaxed: no excitation, no cross-bridge binding (physically covered by trop/trop complex)

Excited: fiber excited, Ca2+ released/binds with troponin, so trop/trop complex moves aside to
expose cross-bridge binding site, cross-bridge binding occurs
Muscle contraction: sliding filament mechanism, cycles of cross-bridge binding/bending pulls
thin filaments in (power stroke), Z lines come closer, sarcomere/muscle shortens/contracts, H-
zone/I-band decrease, A-band unaffected
Binding: myosin cross-bridge binds to actin, power stroke: cross-bridge bends, pulling thin
myofilament inwards; detachment: cross bridge detaches and returns due to association of
second ATP molecule; binding: myosin bridge binds to more distal actin, repeat, asynchronous
Excitation-contraction coupling: muscle excitation linked to contraction, Ca2+:
1) ACH released at NMJ  AP generated in muscle  transverse T tubules/sarcoplasmic
reticulum
2) T tubules: dips of surface membrane into muscle fibers at A/I-band junction, AP travels
rapidly  SPR permeability changes
3) Sarcoplasmic reticulum: modified EPR, forms network around myofibrils, lateral
sacs/terminal cisternae store Ca2+ (to be released by AP), reuptake needs E

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EC coupling: T tubule: foot protein/Ca release channel/ryanodine receptor (open

conformation); lateral sacs of SR: dihydropyridine DHP receptor (blocked)  cytosol lets out Ca;
lumen of T tubule (extracellular space)  voltage-sensitive DHP protein touching ryanodine
receptor  allows Ca from SR lumen into cytosol
Ryanodine receptors: skeletal muscle (physical change, mutate into malignant hyperthermia,
surgery  succinyl choline + halogenated anesthetics), heart (Ca-induced Ca release, mutate
into cardiac arrhythmia), brain
Skeletal muscle contraction: myosin cross bridge turns ATP into ADP + Pi + E, Mg2+ important,
ADP/Pi bound to myosin, energy stored in cross bridge, power stroke on binding of actin 
ADP/Pi released
Rigor mortis: stiffness of skeletal muscles 3-4h after death, peaks at 12h, inability of actin-
myosin complex to dissociate (not enough ATP)
Skeletal muscle relaxation: Ca2+ returns into SPR: no ACH at NMJ terminates AP at muscle cell,
Ca taken up by SPR via Ca ATPase pump, trop/trop complex slips back, actin-myosin can’t bind,
actin back to resting; contractile activity outlast electrical activity: AP lasts 1-2 msec, latent
period between AP/muscle contraction (100 msec) (variable strength)

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Skeletal muscle mechanics: one AP  brief weak contraction twitch too short/weak to be
useful, adjust #muscle fibers contracting (extent of motor unit recruitment), and tension of
each fiber (frequency of stimulation/length/thickness/fatigue) to vary strength
Motor unit: motor neuron and innervated fibers distributed evenly, tension depends on
size/extent of motor unit involvement/size of motor units; fatigue prevented by shifts
(asynchronous recruitment of MUs); large muscles  coarse control; posture: 3 shifts/day
Twitch summation: two twitches added together due to close timing  greater tension than
one alone, duration of AP  resultant twitch discrepancy; (tetanus: smooth sustained

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contraction of maximal strength 3-4x twitch, rapid stimulation of muscle fiber w/no time for
relaxation, from sustained Ca2+ elevation and more CB cycling); so Ca released at start of twitch
and pumped back into SPR at end of twitch
Fiber tension: fiber length at contraction onset (resting length = optimal)  maximal cross-
bridge opportunity, depends on fatigue/thickness; cardiac muscle stretched beyond
actin/myosin capacity  congestive heart failure
Isometric (equal length) contraction: tension < load, can’t shorten and lift with load, no
∆length despite tension development
Isotonic (equal tone) contraction: tension > load, usually shortens/lifts object, ∆length but
constant tension, two types: concentric (shorten, bicep curls) and eccentric (lengthen)

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Skeletal muscle metabolism: contraction/relaxation needs ATP for:

-cross bridge power stroke by myosin ATPase
-detaching cross bridges from actin filaments after power stroke
-transport of Ca back into SPR during relaxation
Additional pathways: from creatinine phosphate/oxidative phosphorylation/glycolysis
3 types of skeletal muscle fibers: oxidative/glycolytic = pathway used to synthesize ATP,
fast/slow = rapidity they split ATP/contract
slow-oxidative type I (red, myoglobin/mitochondria, resist fatigue, back and legs, recruited
first, slow twitch), fast-oxidative IIa (high myosin ATPase activity, red, myoglobin/mitochondria,
recruited last), fast-glycolytic IIb (high myosin ATPase activity, white, little myoglobin, glycogen,
can’t resist fatigue, arms/chest, recruited last, fast twitch)
Smooth muscles: internal contractile organs (walls of hollow organs/tubes) except heart, exert
pressure/forward movement, elongated, spindle shape, A band dark, I band light, thick myosin
longer than skeletal, thin actin more than skeletal (no troponin), intermediate size filaments for
support, cellular arrangement don’t show banding, innervated by para/sympathetic, dense
bodies at Z lines where bundles of actin connect, myosin between them
Smooth muscle contraction: when Ca enters cells from ECF/intracellular stores, Ca release 
signaling cascade  myosin cross bridge movement, myosin light chain can only associate with
Pi group on it (phosphorylated), calmodulin = troponin, combines with Ca then stimulates a
myosin kinase to become active, which then adds Pi to inactive myosin, which can then bind
with actin now that it’s been phosphorylated
Drugs that raise or lower cAMP affect smooth muscle contraction; inactivates myosin kinase
so that phosphorylated myosin is no longer generated to bind with actin
Types of ongoing smooth muscle contractile activity:
Phasic SM (GI tract): bursts, more Ca, more contractile activity, walls of hollow organs
Tonic SM: partially contracted at all times, low RMP -55 to -40 so some VGCCs opened, tone
dependent on Ca levels not AP activity, walls of arterioles  blood pressure
Ca enters smooth muscle via voltage-gated/leak channels, of IP3 from phospholipase C  Ca-
induced calcium release
Types of smooth muscle: based on how it becomes excited

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Single-unit SM: most common, visceral, functional syncytia: gap junctions, AP develops
and spreads to other cells, contract as one unit; myogenic (self-excitable): no nervous
stimulation for contraction: pacemaker cells  AP  spontaneous electrical activity of
pacemaker or slow-wave potentials, phasic or tonic; pacemaker potentials: automatic ion conc
shifts in ECF/ICF  spontaneous depolarization to threshold; slow-wave potentials (GI tract):
alternating hyper/depolarizing swings in potential caused by cyclical rate changes in Na
transport across membrane, AP occurs at depolarization peak if threshold reached
Multi-unit SM: similar to skeletal/smooth, multiple independent units, neurogenic,
phasic only, involuntary ANS

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