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CELL PHYSIOLOGY
By Dr . Husna Maab Haroon
(BDS, RDS,C–Ortho, FCPS PART 1 )
HOMEOSTASIS
• Maintenance of steady state
• ECF = internal environment/ milieu interior , provides nutrients to cell,
More Na ,Cl
• ICF =Fluid inside cell, more K (98%), MORE ACIDIC
• Tears contains more =amino acids
BODY FLUIDS
total body water ( 60%) 42 liters
ICF ECF
2/3rd of TBW 1/3rd of TBW , 20 % , 14 liters
40% interstitial fluid plasma
28 liters 75% of ECF( 3/4th) 25 % of
ECF(1/4TH)
10.5 liters 3.5 liters
MECHANISMS OF HOMEOSTASIS
Positive feedback
• Amplified effect
• Examples
Child birth ( Ferguson reflex)
Clotting
Calcium entry in SR
Generation of nerve signals
Follicular phase of menstrual cycle(LH surge)
Negative feedback
• Maintenance of balanced levels
• Oppose the change
• Examples
BP regulation
Temperature regulation
RELATED MCQS
• ECF differs from ICF = contains more Na and Cl
• ICF 98% K , more acidic
• Main role of negative feedback = brings hormones to normal level
• High in tears than plasma = amino acids
• If 600 ml of water is ingested rapidly plasma volume will increase by = 50 ml
ORGANELLES
• Protoplasm
Water = 70% , proteins =20% , lipids=2% , carbohydrates=1%
Most abundant protein in mammalian cells = actin , largest protein = Tinin
CELL MEMBRANE
• Thickness =7.5nm
• Composition = proteins > lipids > carbohydrates ( mainly phospholipids )
• Ratio of proteins to lipids= 1: 1 , in inner mitochondrial membrane > proteins , in
myelin > lipids
• Fluid mosaic model ( lipid bilayer with embedded proteins )
• Bond= hydrophobic + covalent bond
• Cell membrane fluidity is maintained by = cholesterol
COMPONENTS OF CELL MEMBRANE
Lipids
• Lipid bilayer
• Hydrophilic head , hydrophobic tail
(Amphipathic)
• Lipid soluble substances cross cell
membrane easily ( O2 , CO2 , steroids )
• Water soluble substances cross through
special pores ( Na , Cl , H2O )
Proteins
• Integral proteins
Hydrophobic interactions , embedded in
membrane
• Peripheral proteins
Loosely attached by electrostatic
interactions , not covalently bonded (
correction of Rabia Ali )
SOME TERMS
• Rafts : areas of cell membrane especially rich in cholesterol; and sphingolipids
• Caveolae : rafts are precursors of flask shaped membrane depressions called
caveolae
• Glycocalyx : throughout cell membrane , carbohydrates form loose covering called
glycocalyx .
ORGANELLES(HIGH YIELD POINTS)
Mitochondria
Powerhouse of the cell
Has its own DNA
Self replication
ATP synthesis
Initiation of apoptosis
Contains anticardiolipin
antibody
More mitochondria in cilia
Ribosomes
Protein synthesis
no membrane
Composed of RRNA and
protein
RRNA formed in nucleolus
Polychromasia in
erythropoiesis is due to= Hb
ribosomes
Basophilia due to =ribosomes
Lysosomes
Arise from Golgi apparatus
uterus and breast regress
after pregnancy by lysosomes
Contains hydrolytic enzymes
Hollow structure
Contains acid phosphatases
Causes phagocytosis
MITOCHONDRIA POINTS
• Outer membrane ( more lipids )
• Inner membrane ( more proteins ) , has folding called cristae
• Cristae contains enzymes for oxidative phosphorylation
• Matrix contains enzymes for fatty acid oxidation and TCA cycle
• More in ciliated cell , contains anticardiolipin antibody
• Maternal inheritance
• Initiation of apoptosis ( by cytochrome c which intern activates caspases )
• In oncocytomas large amount of defective mitochondria is found
• Protein proton gradient
LYSOSOMAL STORAGE DISEASES
• Tay sach disease : deficiency of hexosaminidase , causes blindness and mental
retardation
• Pompe disease : deficiency of lysosomal alpha glycosidase
• Lysosomes are also known as suicidal bag of cell
• Lysosomes not present in RBCS
• Have acidic Ph
• Chief marker = acid phosphatases
• Acrosome ( head of sperm) contains lysosomes
ENDOPLASMIC RETICULUM
• Largest organelles
• Nuclear membrane is continuous with RER
ROUGH ENDOPLASMIC RETICULUM
• Contains Ribosomes
• Function ( synthesis of proteins )
• Abundant in pancreatic cells , goblet cells of small intestine
• Basophilia ( ribosomes > RER )
• Nissl bodies are mainly present in =RER
• A cell active in protein synthesis will have dense prominent nucleolus
SMOOTH ENDOPLASMIC RETICULUM
• Functions ( steroids synthesis , fatty acid elongation , detoxification of drugs ,
enzymes for glycogenolysis )
• More in hepatocytes and adrenal cortex
• Intracellular Ca is released by = Sarcoplasmic reticulum
GOLGI APPARATUS /DICTYOSOMES
• Polarized structure ( cis face – closer to nucleus , trans face – closer to membrane )
• Functions
Post translation modification of proteins
Storage and packaging of proteins
Forms glycoproteins by modifying proteins
Form secretary fibers and lysosomes
Fatty acids and glycerol combine in Golgi apparatus
Fatty acids converted to neutral fat
Misfolded proteins formed by Golgi are degraded by
Proteosomes
PEROXISOMES
• Formed by budding from SER
• Microbodies (0.5microns )
• Contain oxidases( for beta – oxidation of long chain fatty acids )
• Contains catalases ,H2O2
• Detoxification of alcohol (peroxisomes), toxic alcohol detoxification( SER)
OTHER ORGANELLES
Centrosomes
In microtubules= 9 centrioles
in triplets( basal bodies in
centrioles)When cell divides
centrosomes duplicate
Nucleus
Double membrane bounded
Nucleolus has no membrane
, contains RNA
In active protein formation
=prominent nucleolus
Nucleolus = site of ribosomal
RNA synthesis
Non membrane
bounded organelles
Microvilli
Cilia (Kartagener syndrome)
Flagella
Ribosomes
Centrioles
Basal bodies
TYPES OF CELL CONNECTIONS
• Tight junctions (zonula occludens ) connects 2 epithelial cells
Occludins, claudins
• Gap junctions ( in Myocardial cells , in smooth muscles ) Heart acts as a syncytium
due to gap junction , connexins
• Adherent junctions ( zona adherens )
• Hemidesmosomes ( integrans , cell to basal lamina ) cell to basement membrane
• Desmosomes ( macula adherens ) cell- cell adhesion ( cadherin , intermediate
filaments , cytoskeleton )
CYTOSKELETON
• Desmin : maintains structural and functional integrity
• Vimentin : attachment, cell signaling ,cell migration
• Cytokeratin :resist mechanical stress ( involve in cell repair )
• Microtubulin : cell division
• ECM to ICM = intermediate filament
• Cytoskeletal to ECM= integrin
TRANSPORT ACROSS CELL MEMBRANE
Passive transport
Simple diffusion
Osmosis
Carrier mediated transport
Facilitated diffusion
Primary active transport
Secondary active transport
SIMPLE DIFFUSION
• Not carrier mediated
• Downhill movement
• Passive
• Diffusion of CO2 from blood to alveoli ,
• If drug weighs < 100 = diffusion , if > 100 /= 100 =pinocytosis
• Depends on thickness of membrane , permeability of membrane, surface area ,
oil/water ratio
• Pulmonary edema
OSMOSIS
• Is the flow of water across a semipermeable membrane from solution with low solute
concentration to the solution with high solute concentration
• Osmolarity is concentration of osmotically active particles in a solution
• Osmolarity = g x C (g = no of particles , C = concentration )
• Colloid osmotic pressure or oncotic pressure is the osmotic pressure created by proteins
• High osmotic pressure = hypertonic , low osmotic pressure= hypotonic
• Reflection coefficient ( the ease with which a solute permeates the membrane ) ( if 0 ,
solute is impermeable , if 1 solute is permeable )
• Effective osmotic pressure ( van’t hoff’s law ) = osmotic pressure x reflection coefficient
CARRIER MEDIATED TRANSPORT
• Stereospecificity ( D –glucose by facilitated diffusion while L glucose is not )
• Saturation ( Vmax)
• Competition ( galactose is a competitive inhibitor of glucose in small intestine )
Facilitated diffusion
• Downhill , requires carrier , rapid than simple diffusion )
• Examples ( facilitated diffusion of glucose across placenta , glucose transport in
muscle and adipose tissue )
• GLUT 4 / DM type 2
ACTIVE TRANSPORT
• Against electrochemical gradient
• Requires ATP ( energy )
• Is carrier mediated ( similarity between facilitated diffusion and active transport )
Primary active transport
• Examples ( NaK-ATPase 3Na / 2K , Ca-ATPase in SR , H-k ATPase )
Secondary active transport
• Co-transport ( Na / glucose Cotransport in small intestine, Na-K -2Cl in ascending limb)
• Glucose and amino acid transport in kidney and small intestine = co transport
• Counter transport ( Na –Ca exchange , Na –H exchange )
IMPORTANT POINTS
• facilitated diffusion of which substance occurs in intestine= fructose
• Gaseous exchange in lung and blood occurs through = passive transport
• Aqueous humor production= active sodium secretion
• 1st step in CSF formation= ultrafiltration of Na
• Glucose absorbed in placenta = by facilitated diffusion
• Active transport requires = pumps , secondary active transport requires = carriers
• Water enters in cells by =pores
• Water enters the extracellular space by= filtration
• All or none response is initiated at = axon hillock
CONT….
• Insulin needed for glucose transport in = skeletal muscles
• Insulin independent glucose transport in = exercising skeletal muscles and BRICK
LIPS ( Brain, RBCs , Intestine, Cornea , Kidney , Liver , Islet cells , Placenta ,
Spermatocytes )
TYPES OF CELLS
• Labile cells ( continuously dividing ) most affected by chemotherapy
Examples( bone marrow , gut epithelium , skin , hair follicles , germ cells
• Stable cells ( divide when injured ) pneumonic HPPL
Examples( hepatocytes , PCT, periosteal cells, lymphocytes)
• Permanent cells (non dividing ) ( pneumonic =SCNR)
Examples ( neurons , skeletal muscles , cardiac muscles, RBCs )
• Olfactory nerve cells repair after every 2 weeks due to = basal cells
ION CHANNELS
• Selective
• May be open or closed
• Gates
Voltage gated channels ( Na channel )
Ligand gated channels ( hormones , second messengers , neurotransmitter ) Ach
MEMBRANE POTENTIALS
• Diffusion potential is the potential difference due to concentration difference of ions
Size depends on concentration gradient , sign depends on sign of diffusing ion
• Equilibrium potential is the potential difference that would balance the
concentration difference
At equilibrium no net diffusion of ions
Na = +60 m volts , K = -m volts , Cl = - 70 m volts 90
RESTING MEMBRANE POTENTIAL
• Is the measured potential difference across cell membrane in millivolts
• RMP of nerve = - 70mvolts , skeletal muscle= - 90m volts , smooth muscles / cardiac
pacemaker cells= - 55 m volts
• Resting membrane potential achieved by = K efflux
• RMP maintained by = Na / K ATPase pump
ACTION POTENTIAL
• Depolarization
Cell anterior becomes less negative
Na influx (inward current )
• Repolarization (anterior become more negative )
K efflux ( outward current)
• Hyperpolarization
K efflux
Plateau ( Ca in while K OUT ) ( in cardiac cells)
IMPORTANT POINTS
• In astrocytes action potential due to = K efflux
• In organ of Corti and utricle = action potential due to= K Influx
• Decrease height of action potential due to = hyponatremia ( in burn patients)
• Excitation of nerve trunk is shown by = compound potential
• Regarding myelinated fibers = action potential at internodes ( internodes contain more Na )
• In Na free environment = no action potential
• Hyperexcitability of nerves occur in = decreased extracellular calcium
• What causes rigor mortis = a decrease in ATP
• Difficult to create action potential = hypokalemia
• In intestine glucose transport by = Na glucose co transport
• Secondary active transport requires carriers
• Local anaesthesia cross placenta by = simple diffusion
REFRACTORY PERIODS
• Absolute refractory period
No action potential can be elicited , inactivation gates of Na closed when membrane is
depolarized
• Relative refractory period
End of absolute refractory period , action potential can be elicited if larger current is
provided
K conductance is higher , membrane potential is closer to K equilibrium potential ,
More threshold is required to initiate action potential
NEUROMUSCULAR JUNCTION
• Synapse between axons of motor neurons and skeletal muscles
• An action potential in presynaptic cell causes depolarization of presynaptic terminal
• As a result , calcium enters causing release of neurotransmitter (Ach ) in synaptic
cleft
• Neurotransmitter combine with receptors in post synaptic membrane causing
change in ion permeability
• excitatory neurotransmitters depolarize and inhibitory neurotransmitters
hyperpolarize the membrane
• 1. Synthesis and storage of ACh in the presynaptic terminal; Choline
acetyltransferase catalyzes the formation of ACh from acetyl coenzyme A (CoA) and
choline in the presynaptic terminal.
acetyl CoA + choline Acetyl choline
• Acetylcholine is stored in synaptic vesicles with ATP and proteoglycan for later
release.
• The postsynaptic membrane potential is depolarized to a value halfway between the
Na+ and K+ equilibrium potentials (approximately 0 mV). The contents of one
synaptic vesicle produce a miniature end plate potential (MEPP), the smallest
possible EPP.
• Degradation of ACh The EPP is transient because ACh is degraded to acetyl CoA and
choline by acetylcholinesterase (AChE) on the muscle end plate. One-half of the choline
is taken back into the presynaptic ending by Na+ -choline cotransport and used to
synthesize new ACh.
• AChE inhibitors (neostigmine) block the degradation of ACh, prolong its action at the
muscle end plate, and increase the size of the EPP.
• Hemicholinium blocks choline reuptake and depletes the presynaptic endings of ACh
stores.
• Disease—myasthenia gravis is caused by the presence of antibodies to the ACh
receptor. is characterized by skeletal muscle weakness and fatigability resulting from a
reduced number of ACh receptors on the muscle end plate. The size of the EPP is
reduced; therefore, it is more difficult to depolarize the muscle membrane to threshold
and to produce action potentials. Treatment with AChE inhibitors (e.g., neostigmine)
prevents the degradation of ACh and prolongs the action of ACh at the muscle end plate,
partially compensating for the reduced number of receptor
SYNAPTIC TRANSMISSION
• . Types of arrangements
• a. One-to-one synapses (such as those found at the neuromuscular junction) An action
potential in the presynaptic element (the motor nerve) produces an action potential in
the postsynaptic element (the muscle).
• b. Many-to-one synapses (such as those found on spinal motoneurons) An action
potential in a single presynaptic cell is insufficient to produce an action potential in the
postsynaptic cell. Instead, many cells synapse on the postsynaptic cell to depolarize it to
threshold.
• A man while working accidently lands his foot on pointed object and immedietely
removed it due to = multisynaptic response
SUMMATION OF SYNAPSES
• a. Spatial summation occurs when two excitatory inputs arrive at a postsynaptic
neuron simultaneously. Together, they produce greater depolarization.
• b. Temporal summation occurs when two excitatory inputs arrive at a postsynaptic
neuron in rapid succession. Because the resulting postsynaptic depolarizations
overlap in time, they add in stepwise fashion.
• Nerve conducting one sensation modality at a time .This is called labelled line
principle.
• Which cells has many dendritic synapses = cerebellar cortex
• Synapses are most likely absent in =dorsal root ganglion
EXCITATORY NEUROTRANSMITTERS
• Depolarizes post synaptic cells , Opening of Na /K channels
• Examples ( Ach , norepinephrine, epinephrine , dopamine , serotonin , glutamate )
1. Norepinephrine is synthesized in the nerve terminal and released into the
synapse to bind with ι or β receptors on the postsynaptic membrane. is removed
from the synapse by reuptake by monoamine oxidase (MAO) and (COMT). The
metabolites are: a. 3,4-Dihydroxymandelic acid (DOMA) b. Normetanephrine
(NMN) c. 3-Methoxy-4-hydroxyphenylglycol (MOPEG) d. 3-Methoxy-4-
hydroxymandelic acid or vanillylmandelic acid (VMA) In pheochromocytoma, a
tumor of the adrenal medulla that secretes catecholamines, urinary excretion of
VMA is increased.
2. 2. Epinephrine is synthesized from norepinephrine by the action of
phenylethanolamine-N-methyltransferase .
CONT/….
1. . Dopamine is prominent in midbrain neurons. is released from the hypothalamus
and inhibits prolactin secretion; is metabolized by MAO and COMT. Parkinson
disease involves degeneration of dopaminergic neurons that use the D2 receptors.
2. . c. Serotonin is present in high concentrations in the brain stem. is formed from
tryptophan(pneumonic=fan). is converted to melatonin in the pineal gland.
3. d. Histamine is formed from histidine. is present in the neurons of the
hypothalamus
INHIBITORY NEUROTRANSMITTERS
• Glycine and GABA
• Hyperpolarize , opening chloride channels
GABA is an inhibitory neurotransmitter. is synthesized from glutamate. has two types of
receptors: (1) The GABA A receptor increases Cl− conductance and is the site of action of
benzodiazepines and barbiturates. (2) The GABA B receptor increases K+ conductance.
Glycine is an inhibitory neurotransmitter found primarily in the spinal cord and brain
stem. increases Cl− conductance.
Nitric oxide (NO) is a short-acting inhibitory neurotransmitter in the gastrointestinal
tract, blood vessels, and the central nervous system. is synthesized in presynaptic nerve
terminals, where NO synthase converts arginine to citrulline and NO.
SKELETAL MUSCLES
• Each muscle fiber is multinucleated . It contains bundles of myofibrils, surrounded by SR and
invaginated by transverse tubules (T tubules). Each myofibril contains interdigitating thick and
thin filaments arranged longitudinally in sarcomeres. A sarcomere runs from Z line to Z line.
• 1. Thick filaments are present in the A band in the center of the sarcomere. contain myosin. a.
Myosin has six polypeptide chains, including one pair of heavy chains and two pairs of light chains.
b. Each myosin molecule has two “heads” attached to a single “tail.” The myosin heads bind ATP
and actin and are involved in cross-bridge formation.
• 2. Thin filaments are anchored at the Z lines. are present in the I bands. contain actin,
tropomyosin, and troponin. a. Troponin is the regulatory protein that permits cross-bridge
formation when it binds Ca2+ . b. Troponin is a complex of three globular proteins: Troponin T (“T”
for tropomyosin) attaches the troponin complex to tropomyosin. Troponin I (“I” for inhibition)
inhibits the interaction of actin and myosin. Troponin C (“C” for Ca2+) is the Ca2+-binding protein
that, when bound to Ca2+, permits the interaction of actin and myosin.
• Actin bound to Z line by actinin .
CONT….
• . T tubules are an extensive tubular network, open to the extracellular space, that carry the
depolarization from the sarcolemmal membrane to the cell interior. are located at the
junctions of A bands and I bands. contain a voltage-sensitive protein called the
dihydropyridine receptor; depolarization causes a conformational change in the
dihydropyridine receptor.
• SR is the internal tubular structure that is the site of Ca2+ storage and release for
excitation–contraction coupling. has terminal cisternae that make intimate contact with the T
tubules in a triad arrangement. membrane contains Ca2+-ATPase (Ca2+ pump), which
transports Ca2+ from intracellular fluid into the SR interior, keeping intracellular [Ca2+] low.
contains Ca2+ bound loosely to calsequestrin. contains a Ca2+ release channel called the
ryanodine receptor.
EXCITATION CONTRACTION COUPLING OF
SKELETAL MUSCLES
• 1. Action potentials in the muscle cell membrane initiate depolarization of the T
tubules
• . 2. Depolarization of the T tubules causes a conformational change in its
dihydropyridine receptor, which opens Ca2+ release channels (ryanodine receptors)
in the nearby SR, causing release of Ca2+ from the SR into the intracellular fluid.
• 3. Intracellular [Ca2+] increases.
• 4. Ca2+ binds to troponin C in the thin filaments, causing a conformational change
in troponin that moves tropomyosin out of the way. The crossbridge cycle begins
EXCITATION – CONTRACTION COUPLING OF
SKELETAL MUSCLES
CROSS BRIDGE FORMATION
• At first, no ATP is bound to myosin (and myosin is tightly attached to actin. In the absence of ATP, this
state is permanent (i.e., rigor).
• ATP then binds to myosin , producing a conformational change in myosin that causes myosin to be
released from actin.
• Myosin is displaced toward the plus end of actin. There is hydrolysis of ATP to ADP and inorganic
phosphate (Pi ). ADP remains attached to myosin (C)
• Myosin attaches to a new site on actin, ADP is then released, returning myosin to its rigor state. The
cycle repeats as long as Ca2+ is bound to troponin
• Each crossbridge cycle “walks” myosin further along the actin filament.
• Relaxation occurs when Ca2+ is reaccumulated by the SR Ca2+-ATPase (SERCA).
• Mechanism of tetanus. A single action potential causes the release of a standard amount of Ca2+ from
the SR and produces a single twitch. However, if the muscle is stimulated repeatedly, more Ca2+ is
released from the SR and there is a cumulative increase in intracellular [Ca2+], extending the time for
cross-bridge cycling. The muscle does not relax (tetanus).
TYPES OF SMOOTH MUSCLES
• 1. Multiunit smooth muscle
is present in the iris, ciliary muscle of the lens, and vas deferens. behaves as separate motor units.
has little or no electrical coupling between cells. is densely innervated; contraction is controlled by
neural innervation (e.g., autonomic nervous system).
2. Unitary (single-unit) smooth muscle
is the most common type and is present in the uterus, gastrointestinal tract, ureter, and bladder. is
spontaneously active (exhibits slow waves) and exhibits “pacemaker” activity which is modulated by
hormones and neurotransmitters. has a high degree of electrical coupling between cells and,
therefore, permits coordinated contraction of the organ (e.g., bladder).
3. Vascular smooth muscle has properties of both multiunit and single-unit smooth muscle.
Pericytes provides support to smooth muscles by which structure = blood vessels
EXCITATION CONTRACTION COUPLING OF
SMOOTH MUSCLES
• There is no troponin; instead, Ca2+ regulates myosin on the thick filaments.
• Depolarization of the cell membrane opens voltage-gated Ca2+ channels and Ca2+
flows into the cell down its electrochemical gradient, increasing the intracellular [Ca2+].
• Hormones and neurotransmitters may open ligand-gated Ca2+ channels in the cell
membrane. Ca2+ entering the cell causes release of more Ca2+ from the SR in a process
called Ca2+ - induced Ca2+ release. Hormones and neurotransmitters also directly
release Ca2+ from the SR through inositol 1,4,5-trisphosphate (IP3 )–gated Ca2+
channels.
• Intracellular [Ca2+] increases.
• Ca2+ binds to calmodulin. The Ca2+–calmodulin complex binds to and activates myosin
light chain kinase. When activated, myosin light chain kinase phosphorylates myosin
and allows it to bind to actin, thus initiating cross-bridge cycling. The amount of tension
produced is proportional to the intracellular Ca2+ concentration.
• A decrease in intracellular [Ca2+] produces relaxation
TYPES OF CONTRACTIONS
• Isometric contractions :
When muscle length does not change , but tension changes during contraction ,
• Isotonic contraction :
When tension does not change, but muscle length changes during contraction .
MUSCLES
Skeletal muscles
Striated
Voluntary
No intercalated disc
Very rapid contractions
Multinucleated
Contains troponin C and forms
Ca- troponin C complex
Contains T tubules
Actin and myosin forms
sarcomere
Smooth muscles
Non striated
Involuntary
No Intercalated disc
Slow contractions
Uni nucleated
Ca – calmodulin complex
Lacks tubules
No sarcomere
Cardiac muscles
Striated
Involuntary
Intercalated disc present
Rapid contractions
Uni nucleated
Ca – troponin C complex
Contains T tubules
Contains sarcomere
SOME IMPORTANT MCQS IN THIS TOPIC
• Skeletal muscles are = innervated by somatic nervous system
• Skeletal muscles = belly is fleshy throughout the length
• Smooth muscles= sustained and slow contractions
• Similarity between cardiac and skeletal muscles = Transverse tubules
• Major difference between cardiac and smooth muscles = nature of contractile protein
• Source of energy in cardiac muscles = fatty acids
• Cardiac muscles cannot be tetanized due to = large refractory period
• Diazepam acts on = internuncial neurons
CELL CYCLE PHASES
• G0 phase ( skeletal muscles ) resting phase
• G 1 phase ( longest phase =8- 10 hours ) RNA , protein, lipid , carbohydrate
synthesis
• S phase ( DNA synthesis ) 5-6 hours
Cytotoxic drugs acts in this phase
• G 2 phase ( ATP synthesis , 3 hours )
• M phase ( shortest phase , 2 hours ) , most sensitive to radiotherapy
Cell division occurs in this phase
STAGES OF M PHASE
• Prophase
Chromatin condenses to form well defined chromosomes , nucleolus disappear,
Chromosomes visible in= prophase
• Metaphase
Chromosomes align at metaphase plate , chromosomes best studied in =metaphase
• Anaphase ( chromosomes moves towards opposite poles )
• Telophase ( chromatin forms, nucleolus reappear )
• Cytokinesis ( cleavage occurs )
BARR BODIES
• X chromosomes
• Heterochromatin
• Absent in Turner’s syndrome (XO )
• One barr body = XX
• 2 barr bodies = XXX
• Are seen in light microscopy
TYPES OF INJURY
Reversible
• Cellular swelling ( due to entry of
extracellular water )
• ER Swelling ( early sign )
• Myelin figures
Irreversible
• Reliable sign= autophagy of cell
• Most imp sign = massive Ca influx
• Membrane damage
• Karyolysis ( fading of DNA)
• Karyorrhexis (nuclear fragmentation )
• Pyknosis ( Chromatin shrinkage )
• Apoptosis
• Necrosis
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Cell physiology for dentistry fcps1.pptx

  • 1.
  • 2. CELL PHYSIOLOGY By Dr . Husna Maab Haroon (BDS, RDS,C–Ortho, FCPS PART 1 )
  • 3. HOMEOSTASIS • Maintenance of steady state • ECF = internal environment/ milieu interior , provides nutrients to cell, More Na ,Cl • ICF =Fluid inside cell, more K (98%), MORE ACIDIC • Tears contains more =amino acids
  • 4. BODY FLUIDS total body water ( 60%) 42 liters ICF ECF 2/3rd of TBW 1/3rd of TBW , 20 % , 14 liters 40% interstitial fluid plasma 28 liters 75% of ECF( 3/4th) 25 % of ECF(1/4TH) 10.5 liters 3.5 liters
  • 5. MECHANISMS OF HOMEOSTASIS Positive feedback • Amplified effect • Examples Child birth ( Ferguson reflex) Clotting Calcium entry in SR Generation of nerve signals Follicular phase of menstrual cycle(LH surge) Negative feedback • Maintenance of balanced levels • Oppose the change • Examples BP regulation Temperature regulation
  • 6.
  • 7. RELATED MCQS • ECF differs from ICF = contains more Na and Cl • ICF 98% K , more acidic • Main role of negative feedback = brings hormones to normal level • High in tears than plasma = amino acids • If 600 ml of water is ingested rapidly plasma volume will increase by = 50 ml
  • 8. ORGANELLES • Protoplasm Water = 70% , proteins =20% , lipids=2% , carbohydrates=1% Most abundant protein in mammalian cells = actin , largest protein = Tinin
  • 9. CELL MEMBRANE • Thickness =7.5nm • Composition = proteins > lipids > carbohydrates ( mainly phospholipids ) • Ratio of proteins to lipids= 1: 1 , in inner mitochondrial membrane > proteins , in myelin > lipids • Fluid mosaic model ( lipid bilayer with embedded proteins ) • Bond= hydrophobic + covalent bond • Cell membrane fluidity is maintained by = cholesterol
  • 10.
  • 11. COMPONENTS OF CELL MEMBRANE Lipids • Lipid bilayer • Hydrophilic head , hydrophobic tail (Amphipathic) • Lipid soluble substances cross cell membrane easily ( O2 , CO2 , steroids ) • Water soluble substances cross through special pores ( Na , Cl , H2O ) Proteins • Integral proteins Hydrophobic interactions , embedded in membrane • Peripheral proteins Loosely attached by electrostatic interactions , not covalently bonded ( correction of Rabia Ali )
  • 12.
  • 13. SOME TERMS • Rafts : areas of cell membrane especially rich in cholesterol; and sphingolipids • Caveolae : rafts are precursors of flask shaped membrane depressions called caveolae • Glycocalyx : throughout cell membrane , carbohydrates form loose covering called glycocalyx .
  • 14. ORGANELLES(HIGH YIELD POINTS) Mitochondria Powerhouse of the cell Has its own DNA Self replication ATP synthesis Initiation of apoptosis Contains anticardiolipin antibody More mitochondria in cilia Ribosomes Protein synthesis no membrane Composed of RRNA and protein RRNA formed in nucleolus Polychromasia in erythropoiesis is due to= Hb ribosomes Basophilia due to =ribosomes Lysosomes Arise from Golgi apparatus uterus and breast regress after pregnancy by lysosomes Contains hydrolytic enzymes Hollow structure Contains acid phosphatases Causes phagocytosis
  • 15. MITOCHONDRIA POINTS • Outer membrane ( more lipids ) • Inner membrane ( more proteins ) , has folding called cristae • Cristae contains enzymes for oxidative phosphorylation • Matrix contains enzymes for fatty acid oxidation and TCA cycle • More in ciliated cell , contains anticardiolipin antibody • Maternal inheritance • Initiation of apoptosis ( by cytochrome c which intern activates caspases ) • In oncocytomas large amount of defective mitochondria is found • Protein proton gradient
  • 16.
  • 17. LYSOSOMAL STORAGE DISEASES • Tay sach disease : deficiency of hexosaminidase , causes blindness and mental retardation • Pompe disease : deficiency of lysosomal alpha glycosidase • Lysosomes are also known as suicidal bag of cell • Lysosomes not present in RBCS • Have acidic Ph • Chief marker = acid phosphatases • Acrosome ( head of sperm) contains lysosomes
  • 18. ENDOPLASMIC RETICULUM • Largest organelles • Nuclear membrane is continuous with RER ROUGH ENDOPLASMIC RETICULUM • Contains Ribosomes • Function ( synthesis of proteins ) • Abundant in pancreatic cells , goblet cells of small intestine • Basophilia ( ribosomes > RER ) • Nissl bodies are mainly present in =RER • A cell active in protein synthesis will have dense prominent nucleolus
  • 19. SMOOTH ENDOPLASMIC RETICULUM • Functions ( steroids synthesis , fatty acid elongation , detoxification of drugs , enzymes for glycogenolysis ) • More in hepatocytes and adrenal cortex • Intracellular Ca is released by = Sarcoplasmic reticulum
  • 20. GOLGI APPARATUS /DICTYOSOMES • Polarized structure ( cis face – closer to nucleus , trans face – closer to membrane ) • Functions Post translation modification of proteins Storage and packaging of proteins Forms glycoproteins by modifying proteins Form secretary fibers and lysosomes Fatty acids and glycerol combine in Golgi apparatus Fatty acids converted to neutral fat Misfolded proteins formed by Golgi are degraded by Proteosomes
  • 21. PEROXISOMES • Formed by budding from SER • Microbodies (0.5microns ) • Contain oxidases( for beta – oxidation of long chain fatty acids ) • Contains catalases ,H2O2 • Detoxification of alcohol (peroxisomes), toxic alcohol detoxification( SER)
  • 22. OTHER ORGANELLES Centrosomes In microtubules= 9 centrioles in triplets( basal bodies in centrioles)When cell divides centrosomes duplicate Nucleus Double membrane bounded Nucleolus has no membrane , contains RNA In active protein formation =prominent nucleolus Nucleolus = site of ribosomal RNA synthesis Non membrane bounded organelles Microvilli Cilia (Kartagener syndrome) Flagella Ribosomes Centrioles Basal bodies
  • 23. TYPES OF CELL CONNECTIONS • Tight junctions (zonula occludens ) connects 2 epithelial cells Occludins, claudins • Gap junctions ( in Myocardial cells , in smooth muscles ) Heart acts as a syncytium due to gap junction , connexins • Adherent junctions ( zona adherens ) • Hemidesmosomes ( integrans , cell to basal lamina ) cell to basement membrane • Desmosomes ( macula adherens ) cell- cell adhesion ( cadherin , intermediate filaments , cytoskeleton )
  • 24.
  • 25. CYTOSKELETON • Desmin : maintains structural and functional integrity • Vimentin : attachment, cell signaling ,cell migration • Cytokeratin :resist mechanical stress ( involve in cell repair ) • Microtubulin : cell division • ECM to ICM = intermediate filament • Cytoskeletal to ECM= integrin
  • 26. TRANSPORT ACROSS CELL MEMBRANE Passive transport Simple diffusion Osmosis Carrier mediated transport Facilitated diffusion Primary active transport Secondary active transport
  • 27. SIMPLE DIFFUSION • Not carrier mediated • Downhill movement • Passive • Diffusion of CO2 from blood to alveoli , • If drug weighs < 100 = diffusion , if > 100 /= 100 =pinocytosis • Depends on thickness of membrane , permeability of membrane, surface area , oil/water ratio • Pulmonary edema
  • 28. OSMOSIS • Is the flow of water across a semipermeable membrane from solution with low solute concentration to the solution with high solute concentration • Osmolarity is concentration of osmotically active particles in a solution • Osmolarity = g x C (g = no of particles , C = concentration ) • Colloid osmotic pressure or oncotic pressure is the osmotic pressure created by proteins • High osmotic pressure = hypertonic , low osmotic pressure= hypotonic • Reflection coefficient ( the ease with which a solute permeates the membrane ) ( if 0 , solute is impermeable , if 1 solute is permeable ) • Effective osmotic pressure ( van’t hoff’s law ) = osmotic pressure x reflection coefficient
  • 29. CARRIER MEDIATED TRANSPORT • Stereospecificity ( D –glucose by facilitated diffusion while L glucose is not ) • Saturation ( Vmax) • Competition ( galactose is a competitive inhibitor of glucose in small intestine ) Facilitated diffusion • Downhill , requires carrier , rapid than simple diffusion ) • Examples ( facilitated diffusion of glucose across placenta , glucose transport in muscle and adipose tissue ) • GLUT 4 / DM type 2
  • 30. ACTIVE TRANSPORT • Against electrochemical gradient • Requires ATP ( energy ) • Is carrier mediated ( similarity between facilitated diffusion and active transport ) Primary active transport • Examples ( NaK-ATPase 3Na / 2K , Ca-ATPase in SR , H-k ATPase ) Secondary active transport • Co-transport ( Na / glucose Cotransport in small intestine, Na-K -2Cl in ascending limb) • Glucose and amino acid transport in kidney and small intestine = co transport • Counter transport ( Na –Ca exchange , Na –H exchange )
  • 31.
  • 32. IMPORTANT POINTS • facilitated diffusion of which substance occurs in intestine= fructose • Gaseous exchange in lung and blood occurs through = passive transport • Aqueous humor production= active sodium secretion • 1st step in CSF formation= ultrafiltration of Na • Glucose absorbed in placenta = by facilitated diffusion • Active transport requires = pumps , secondary active transport requires = carriers • Water enters in cells by =pores • Water enters the extracellular space by= filtration • All or none response is initiated at = axon hillock
  • 33. CONT…. • Insulin needed for glucose transport in = skeletal muscles • Insulin independent glucose transport in = exercising skeletal muscles and BRICK LIPS ( Brain, RBCs , Intestine, Cornea , Kidney , Liver , Islet cells , Placenta , Spermatocytes )
  • 34. TYPES OF CELLS • Labile cells ( continuously dividing ) most affected by chemotherapy Examples( bone marrow , gut epithelium , skin , hair follicles , germ cells • Stable cells ( divide when injured ) pneumonic HPPL Examples( hepatocytes , PCT, periosteal cells, lymphocytes) • Permanent cells (non dividing ) ( pneumonic =SCNR) Examples ( neurons , skeletal muscles , cardiac muscles, RBCs ) • Olfactory nerve cells repair after every 2 weeks due to = basal cells
  • 35. ION CHANNELS • Selective • May be open or closed • Gates Voltage gated channels ( Na channel ) Ligand gated channels ( hormones , second messengers , neurotransmitter ) Ach
  • 36. MEMBRANE POTENTIALS • Diffusion potential is the potential difference due to concentration difference of ions Size depends on concentration gradient , sign depends on sign of diffusing ion • Equilibrium potential is the potential difference that would balance the concentration difference At equilibrium no net diffusion of ions Na = +60 m volts , K = -m volts , Cl = - 70 m volts 90
  • 37. RESTING MEMBRANE POTENTIAL • Is the measured potential difference across cell membrane in millivolts • RMP of nerve = - 70mvolts , skeletal muscle= - 90m volts , smooth muscles / cardiac pacemaker cells= - 55 m volts • Resting membrane potential achieved by = K efflux • RMP maintained by = Na / K ATPase pump
  • 38.
  • 39. ACTION POTENTIAL • Depolarization Cell anterior becomes less negative Na influx (inward current ) • Repolarization (anterior become more negative ) K efflux ( outward current) • Hyperpolarization K efflux Plateau ( Ca in while K OUT ) ( in cardiac cells)
  • 40.
  • 41. IMPORTANT POINTS • In astrocytes action potential due to = K efflux • In organ of Corti and utricle = action potential due to= K Influx • Decrease height of action potential due to = hyponatremia ( in burn patients) • Excitation of nerve trunk is shown by = compound potential • Regarding myelinated fibers = action potential at internodes ( internodes contain more Na ) • In Na free environment = no action potential • Hyperexcitability of nerves occur in = decreased extracellular calcium • What causes rigor mortis = a decrease in ATP • Difficult to create action potential = hypokalemia • In intestine glucose transport by = Na glucose co transport • Secondary active transport requires carriers • Local anaesthesia cross placenta by = simple diffusion
  • 42. REFRACTORY PERIODS • Absolute refractory period No action potential can be elicited , inactivation gates of Na closed when membrane is depolarized • Relative refractory period End of absolute refractory period , action potential can be elicited if larger current is provided K conductance is higher , membrane potential is closer to K equilibrium potential , More threshold is required to initiate action potential
  • 43. NEUROMUSCULAR JUNCTION • Synapse between axons of motor neurons and skeletal muscles • An action potential in presynaptic cell causes depolarization of presynaptic terminal • As a result , calcium enters causing release of neurotransmitter (Ach ) in synaptic cleft • Neurotransmitter combine with receptors in post synaptic membrane causing change in ion permeability • excitatory neurotransmitters depolarize and inhibitory neurotransmitters hyperpolarize the membrane
  • 44.
  • 45. • 1. Synthesis and storage of ACh in the presynaptic terminal; Choline acetyltransferase catalyzes the formation of ACh from acetyl coenzyme A (CoA) and choline in the presynaptic terminal. acetyl CoA + choline Acetyl choline • Acetylcholine is stored in synaptic vesicles with ATP and proteoglycan for later release. • The postsynaptic membrane potential is depolarized to a value halfway between the Na+ and K+ equilibrium potentials (approximately 0 mV). The contents of one synaptic vesicle produce a miniature end plate potential (MEPP), the smallest possible EPP.
  • 46. • Degradation of ACh The EPP is transient because ACh is degraded to acetyl CoA and choline by acetylcholinesterase (AChE) on the muscle end plate. One-half of the choline is taken back into the presynaptic ending by Na+ -choline cotransport and used to synthesize new ACh. • AChE inhibitors (neostigmine) block the degradation of ACh, prolong its action at the muscle end plate, and increase the size of the EPP. • Hemicholinium blocks choline reuptake and depletes the presynaptic endings of ACh stores. • Disease—myasthenia gravis is caused by the presence of antibodies to the ACh receptor. is characterized by skeletal muscle weakness and fatigability resulting from a reduced number of ACh receptors on the muscle end plate. The size of the EPP is reduced; therefore, it is more difficult to depolarize the muscle membrane to threshold and to produce action potentials. Treatment with AChE inhibitors (e.g., neostigmine) prevents the degradation of ACh and prolongs the action of ACh at the muscle end plate, partially compensating for the reduced number of receptor
  • 47. SYNAPTIC TRANSMISSION • . Types of arrangements • a. One-to-one synapses (such as those found at the neuromuscular junction) An action potential in the presynaptic element (the motor nerve) produces an action potential in the postsynaptic element (the muscle). • b. Many-to-one synapses (such as those found on spinal motoneurons) An action potential in a single presynaptic cell is insufficient to produce an action potential in the postsynaptic cell. Instead, many cells synapse on the postsynaptic cell to depolarize it to threshold. • A man while working accidently lands his foot on pointed object and immedietely removed it due to = multisynaptic response
  • 48. SUMMATION OF SYNAPSES • a. Spatial summation occurs when two excitatory inputs arrive at a postsynaptic neuron simultaneously. Together, they produce greater depolarization. • b. Temporal summation occurs when two excitatory inputs arrive at a postsynaptic neuron in rapid succession. Because the resulting postsynaptic depolarizations overlap in time, they add in stepwise fashion. • Nerve conducting one sensation modality at a time .This is called labelled line principle. • Which cells has many dendritic synapses = cerebellar cortex • Synapses are most likely absent in =dorsal root ganglion
  • 49. EXCITATORY NEUROTRANSMITTERS • Depolarizes post synaptic cells , Opening of Na /K channels • Examples ( Ach , norepinephrine, epinephrine , dopamine , serotonin , glutamate ) 1. Norepinephrine is synthesized in the nerve terminal and released into the synapse to bind with Îą or β receptors on the postsynaptic membrane. is removed from the synapse by reuptake by monoamine oxidase (MAO) and (COMT). The metabolites are: a. 3,4-Dihydroxymandelic acid (DOMA) b. Normetanephrine (NMN) c. 3-Methoxy-4-hydroxyphenylglycol (MOPEG) d. 3-Methoxy-4- hydroxymandelic acid or vanillylmandelic acid (VMA) In pheochromocytoma, a tumor of the adrenal medulla that secretes catecholamines, urinary excretion of VMA is increased. 2. 2. Epinephrine is synthesized from norepinephrine by the action of phenylethanolamine-N-methyltransferase .
  • 50. CONT/…. 1. . Dopamine is prominent in midbrain neurons. is released from the hypothalamus and inhibits prolactin secretion; is metabolized by MAO and COMT. Parkinson disease involves degeneration of dopaminergic neurons that use the D2 receptors. 2. . c. Serotonin is present in high concentrations in the brain stem. is formed from tryptophan(pneumonic=fan). is converted to melatonin in the pineal gland. 3. d. Histamine is formed from histidine. is present in the neurons of the hypothalamus
  • 51. INHIBITORY NEUROTRANSMITTERS • Glycine and GABA • Hyperpolarize , opening chloride channels GABA is an inhibitory neurotransmitter. is synthesized from glutamate. has two types of receptors: (1) The GABA A receptor increases Cl− conductance and is the site of action of benzodiazepines and barbiturates. (2) The GABA B receptor increases K+ conductance. Glycine is an inhibitory neurotransmitter found primarily in the spinal cord and brain stem. increases Cl− conductance. Nitric oxide (NO) is a short-acting inhibitory neurotransmitter in the gastrointestinal tract, blood vessels, and the central nervous system. is synthesized in presynaptic nerve terminals, where NO synthase converts arginine to citrulline and NO.
  • 52. SKELETAL MUSCLES • Each muscle fiber is multinucleated . It contains bundles of myofibrils, surrounded by SR and invaginated by transverse tubules (T tubules). Each myofibril contains interdigitating thick and thin filaments arranged longitudinally in sarcomeres. A sarcomere runs from Z line to Z line. • 1. Thick filaments are present in the A band in the center of the sarcomere. contain myosin. a. Myosin has six polypeptide chains, including one pair of heavy chains and two pairs of light chains. b. Each myosin molecule has two “heads” attached to a single “tail.” The myosin heads bind ATP and actin and are involved in cross-bridge formation. • 2. Thin filaments are anchored at the Z lines. are present in the I bands. contain actin, tropomyosin, and troponin. a. Troponin is the regulatory protein that permits cross-bridge formation when it binds Ca2+ . b. Troponin is a complex of three globular proteins: Troponin T (“T” for tropomyosin) attaches the troponin complex to tropomyosin. Troponin I (“I” for inhibition) inhibits the interaction of actin and myosin. Troponin C (“C” for Ca2+) is the Ca2+-binding protein that, when bound to Ca2+, permits the interaction of actin and myosin. • Actin bound to Z line by actinin .
  • 53. CONT…. • . T tubules are an extensive tubular network, open to the extracellular space, that carry the depolarization from the sarcolemmal membrane to the cell interior. are located at the junctions of A bands and I bands. contain a voltage-sensitive protein called the dihydropyridine receptor; depolarization causes a conformational change in the dihydropyridine receptor. • SR is the internal tubular structure that is the site of Ca2+ storage and release for excitation–contraction coupling. has terminal cisternae that make intimate contact with the T tubules in a triad arrangement. membrane contains Ca2+-ATPase (Ca2+ pump), which transports Ca2+ from intracellular fluid into the SR interior, keeping intracellular [Ca2+] low. contains Ca2+ bound loosely to calsequestrin. contains a Ca2+ release channel called the ryanodine receptor.
  • 54.
  • 55.
  • 56. EXCITATION CONTRACTION COUPLING OF SKELETAL MUSCLES • 1. Action potentials in the muscle cell membrane initiate depolarization of the T tubules • . 2. Depolarization of the T tubules causes a conformational change in its dihydropyridine receptor, which opens Ca2+ release channels (ryanodine receptors) in the nearby SR, causing release of Ca2+ from the SR into the intracellular fluid. • 3. Intracellular [Ca2+] increases. • 4. Ca2+ binds to troponin C in the thin filaments, causing a conformational change in troponin that moves tropomyosin out of the way. The crossbridge cycle begins
  • 57. EXCITATION – CONTRACTION COUPLING OF SKELETAL MUSCLES
  • 58. CROSS BRIDGE FORMATION • At first, no ATP is bound to myosin (and myosin is tightly attached to actin. In the absence of ATP, this state is permanent (i.e., rigor). • ATP then binds to myosin , producing a conformational change in myosin that causes myosin to be released from actin. • Myosin is displaced toward the plus end of actin. There is hydrolysis of ATP to ADP and inorganic phosphate (Pi ). ADP remains attached to myosin (C) • Myosin attaches to a new site on actin, ADP is then released, returning myosin to its rigor state. The cycle repeats as long as Ca2+ is bound to troponin • Each crossbridge cycle “walks” myosin further along the actin filament. • Relaxation occurs when Ca2+ is reaccumulated by the SR Ca2+-ATPase (SERCA). • Mechanism of tetanus. A single action potential causes the release of a standard amount of Ca2+ from the SR and produces a single twitch. However, if the muscle is stimulated repeatedly, more Ca2+ is released from the SR and there is a cumulative increase in intracellular [Ca2+], extending the time for cross-bridge cycling. The muscle does not relax (tetanus).
  • 59.
  • 60. TYPES OF SMOOTH MUSCLES • 1. Multiunit smooth muscle is present in the iris, ciliary muscle of the lens, and vas deferens. behaves as separate motor units. has little or no electrical coupling between cells. is densely innervated; contraction is controlled by neural innervation (e.g., autonomic nervous system). 2. Unitary (single-unit) smooth muscle is the most common type and is present in the uterus, gastrointestinal tract, ureter, and bladder. is spontaneously active (exhibits slow waves) and exhibits “pacemaker” activity which is modulated by hormones and neurotransmitters. has a high degree of electrical coupling between cells and, therefore, permits coordinated contraction of the organ (e.g., bladder). 3. Vascular smooth muscle has properties of both multiunit and single-unit smooth muscle. Pericytes provides support to smooth muscles by which structure = blood vessels
  • 61. EXCITATION CONTRACTION COUPLING OF SMOOTH MUSCLES • There is no troponin; instead, Ca2+ regulates myosin on the thick filaments. • Depolarization of the cell membrane opens voltage-gated Ca2+ channels and Ca2+ flows into the cell down its electrochemical gradient, increasing the intracellular [Ca2+]. • Hormones and neurotransmitters may open ligand-gated Ca2+ channels in the cell membrane. Ca2+ entering the cell causes release of more Ca2+ from the SR in a process called Ca2+ - induced Ca2+ release. Hormones and neurotransmitters also directly release Ca2+ from the SR through inositol 1,4,5-trisphosphate (IP3 )–gated Ca2+ channels. • Intracellular [Ca2+] increases. • Ca2+ binds to calmodulin. The Ca2+–calmodulin complex binds to and activates myosin light chain kinase. When activated, myosin light chain kinase phosphorylates myosin and allows it to bind to actin, thus initiating cross-bridge cycling. The amount of tension produced is proportional to the intracellular Ca2+ concentration. • A decrease in intracellular [Ca2+] produces relaxation
  • 62.
  • 63. TYPES OF CONTRACTIONS • Isometric contractions : When muscle length does not change , but tension changes during contraction , • Isotonic contraction : When tension does not change, but muscle length changes during contraction .
  • 64. MUSCLES Skeletal muscles Striated Voluntary No intercalated disc Very rapid contractions Multinucleated Contains troponin C and forms Ca- troponin C complex Contains T tubules Actin and myosin forms sarcomere Smooth muscles Non striated Involuntary No Intercalated disc Slow contractions Uni nucleated Ca – calmodulin complex Lacks tubules No sarcomere Cardiac muscles Striated Involuntary Intercalated disc present Rapid contractions Uni nucleated Ca – troponin C complex Contains T tubules Contains sarcomere
  • 65. SOME IMPORTANT MCQS IN THIS TOPIC • Skeletal muscles are = innervated by somatic nervous system • Skeletal muscles = belly is fleshy throughout the length • Smooth muscles= sustained and slow contractions • Similarity between cardiac and skeletal muscles = Transverse tubules • Major difference between cardiac and smooth muscles = nature of contractile protein • Source of energy in cardiac muscles = fatty acids • Cardiac muscles cannot be tetanized due to = large refractory period • Diazepam acts on = internuncial neurons
  • 66. CELL CYCLE PHASES • G0 phase ( skeletal muscles ) resting phase • G 1 phase ( longest phase =8- 10 hours ) RNA , protein, lipid , carbohydrate synthesis • S phase ( DNA synthesis ) 5-6 hours Cytotoxic drugs acts in this phase • G 2 phase ( ATP synthesis , 3 hours ) • M phase ( shortest phase , 2 hours ) , most sensitive to radiotherapy Cell division occurs in this phase
  • 67. STAGES OF M PHASE • Prophase Chromatin condenses to form well defined chromosomes , nucleolus disappear, Chromosomes visible in= prophase • Metaphase Chromosomes align at metaphase plate , chromosomes best studied in =metaphase • Anaphase ( chromosomes moves towards opposite poles ) • Telophase ( chromatin forms, nucleolus reappear ) • Cytokinesis ( cleavage occurs )
  • 68. BARR BODIES • X chromosomes • Heterochromatin • Absent in Turner’s syndrome (XO ) • One barr body = XX • 2 barr bodies = XXX • Are seen in light microscopy
  • 69. TYPES OF INJURY Reversible • Cellular swelling ( due to entry of extracellular water ) • ER Swelling ( early sign ) • Myelin figures Irreversible • Reliable sign= autophagy of cell • Most imp sign = massive Ca influx • Membrane damage • Karyolysis ( fading of DNA) • Karyorrhexis (nuclear fragmentation ) • Pyknosis ( Chromatin shrinkage ) • Apoptosis • Necrosis