Prof' Dr' Nurten GALIP

1
Prof. Dr. Nurten GALIP

• FIZYOLOJI A.B.D

2

• FIZYOLOJIYE
• GIRIS

3

• Evrendeki canlilar genel Biyoloji kapsaminda
  incelenir.
• Biyolojiye ait anabilim dallari
• Morfoloji
• Anatomi canliya biçimsel yönden
  yaklasir.Canliyi olusturan kemik, kas ve sinir
  gibi dokulari
• Histoloji bedeni olusturan tüm dokularin
  ince yapilarini
• Embriyoloji embriyo ve gelisimi sirasinda
  olusan degisiklikleri
• Sitoloji Bedeni olusturan çok
  farkli hücre gruplarini inceler.

4

• Fizyoloji ise canlilik sirasinda bedende
  sürdürülen görevleri canliya zarar vermeden dogal
  halinde inceler.Fizyoloji, physis ( yasam) ve
  logos (bilim) terimlerinden olusmustur.
• Canlilik olaylari tek basina incelenemez.Farkli
  fiziksel ve kimyasal kurallar canlilik olaylari
  ile iç içedir. Buna göre fizyoloji, fizik, kimya,
  biyokimya, radyoloji ve patoloji gibi bir çok
  bilim daliyla iliskilidir.
• Insan, hayvan, bitki, bakteri ve virus
  fizyolojisi ile karsilastirmali fizyoloji
  siniflandirilmasi yapilabilir.

5

• Temel Kavramlar

6
Diffüzyon

• Iyon ve moleküllerin sivi veya gaz ortamda
  sürekli hareketlerine diffüzyon (yayilma) denir.
  Ortamda molekül yogunlugu esitleninceye kadar
  yayilma olayi devam eder. Maddenin sivi veya gaz
  ortamda yayilmasi yogunluk farkina (Konsantrasyon
  gradyani) bagli olarak degisir.Yogunluk farki ne
  kadar ise yayilma hizi da o kadar yüksektir.
• Diffüzyon olayinda isi da önemli bir
  etkendir. Çaplari küçük olan molleküler büyüklere
  oranla daha hizli yayilir. Besin maddelerinin
  dokulara, oksijenin alveolden kana ve ilaçlarin
  enjekte edildikleri yerden çevreye geçmelerinde
  diffüzyon olayi önemli bir yer tutar.

7
diffüzyon
8
PASSIVE DIFFUSION THROUGH A MEMBRANE - CASE 1 
no receptor
9
Hemodiyaliz

• Farkli düzeneklerle hasta kani ve diyaliz sivisi
  yari geçirgen bir zar ile temas haline
  getirilir. Bu yari geçirgen bir zar ( hemodiyaliz
  memrani) üzerindeki mikroskopik delikler (por)
  su, sodyum, potasyum, üre gibi küçük moleküllü
  maddeleri bir taraftan diger tarafa difüzyonla
  geçirirken daha büyük moleküllü protein gibi
  diger maddeler ile kan hücrelerini (çaplari
  porlardan daha büyük oldugundan) geçirmezler.
• Üre, kreatinin, fosfor ve daha bir çok üremik
  toksin membrandan diyaliz sivisina geçer,böylece
  kan temizlenir. Diyaliz sivisi kan
  konsantrasyonlarina esit miktarlarda solüt adi
  verilen küçük moleküllü maddeler içerir.
  Difüzyon hizi ve yönüne etkili 3 faktör
• Konsantrasyon gradienti Molekül konsantrasyonu
  artarsa, titreserek, membrana çarpip porlardan
  karsi tarafa geçecek molekül sayisi da o kadar
  artacaktir.
• Molekül agirligi Üre, kreatininden daha küçük
  M.A.oldugundan daha hizla diyaliz edilir.
• Membran direnci Membran kalinligi , porlarinin
  büyüklügü ve sayisi memranin madde alisverisine
  karsi direnci degistirir.

10
Ultrafiltrasyon

• Su molekülleri (molekül agirligi küçük oldugu
  için) diyaliz membranindan kolayca geçer. Su ile
  içinde erimis olan bazi solütler de geçer. Bu
  olaya ultrafiltrasyon denir.Burada 2 önemli
  faktör rol alir.Birincisi hidrostatik
  basinçtir,ikincisi ozmotik basinçtir.
• Ozmotik basinç, solüt konsantrasyonu ile artar.
  Örnegin hemodiyalizde, diyaliz sivisinin ozmotik
  basincini artirirsak (sodyum miktarini
  artirarak), hasta kanindan diyalizata o kadar
  fazla su geçer.

11
Kolaylastirilmis diffüzyon

• Bazen yogunluk ve isi farki olmasina ragmen
  bazi maddeler geçirgen olan zarlardan karsi
  tarafa dog-rudan geçemezler. Bu zardan dogrudan
  geçeme-yen bir maddenin tasiyici denilen (T) bir
  molekül ile birlesip karsi tarafa geçisi
  kolaylastirilmis diffüzyon olarak tanimlanir.
  Örnegin, glikoz molekülü hücre zarinda bulunan
  tasiyici ile birlesip hücre içine girer.

12
FACILITATED DIFFUSION THROUGH MEMBRANE - CASE 2 
receptor-mediated.

13
(No Transcript)
14
Kolaylastirilmis difüzyon
15
Facilitated Diffusion of Molecules

• example The plasma membrane of human red blood
  cells contain transmembrane proteins that permit
  the diffusion of glucose from the blood into the
  cell.
• Note that in all cases of facilitated diffusion
  through channels, the channels are selective
  that is, the structure of the protein admits only
  certain types of molecules through
• Whether all cases of facilitated diffusion of
  small molecules use channels is yet to be proven.
  Perhaps some molecules are passed through the
  membrane by a conformational change in the shape
  of the transmembrane protein when it binds the
  molecule to be transported.

16
(No Transcript)
17
Facilitated diffusion

• Facilitated diffusion is a process whereby a
  substance passes through a membrane with a aid of
  an intermediary or a facilitator. The facilitator
  is an integral membrane protein that spans the
  width of the membrane. The force that drives the
  molecule from one side of the membrane to the
  other is the force of diffusion.
• In the figure below K ions are passing through a
  membrane using a potassium transport protein. The
  ions are moving down a concentration gradient so
  the process is a diffusion of K ions.
• Transport proteins are very specific with respect
  to the kinds of molecules or ions that will be
  transported. For example a Na transport protein
  transports Ka ions much better than it will
  transport K ions.

• Transport Proteins

18

• Facilitated Diffusion
• Transmembrane proteins form a channel through the
  cell membrane
• Ions pass down a concentration gradient
• The channel can be opened or closed
• Does not require energy (ATP)
• Ion channel proteins move ions by facilitated
  diffusion

19
Facilitated Diffusion of Ions
20

• External ligands (shown here in green) bind to a
  site on the extracellular side of the channel.
• Acetylcholine.The binding of theneurotransmitter
  acetylcholine at certain synapses opens channels
  that admit Na and initiate a nerve impulse or
  muscle contraction.
• Gamma amino butyric acid (GABA). Binding of GABA
  at certain synapses designated GABAA in the
  central nervous system admits Cl- ions into the
  cell and inhibits the creation of a nerve
  impulse.

21

• Internal ligands
• Internal ligands bind to a site on the channel
  protein exposed to the cytosol.
• Examples
• "Second messengers", like cyclic AMP (cAMP) and
  cyclic GMP (cGMP), regulate channels involved in
  the initiation of impulses in neurons responding
  to odors (koku) and light respectively.
• ATP is needed to open the channel that allows
  chloride (Cl-) and bicarbonate (HCO3-) ions out
  of the cell. This channel is defective in
  patients with cystic fibrosis. Although the
  energy liberated by the hydrolysis of ATP is
  needed to open the channel, this is not an
  example of active transport the ions diffuse
  through the open channel following their
  concentration gradient.

22

• Mechanically-gated ion channels
• Examples
• Sound waves bending the cilia-like projections on
  the hair cells of the inner ear open up ion
  channels leading to the creation of nerve
  impulses that the brain interprets as sound.

23

• Voltage-gated ion channels
• In so-called excitable cells like neuron and
  muscle cells, some channels open or close in
  response to changes in the charge (measured in
  volts) across the plasma membrane.
• Example As an impulse passes down a neuron, the
  reduction in the voltage opens sodium channels in
  the adjacent portion of the membrane. This allows
  the influx of Na into the neuron and thus the
  continuation of the nerve impulse. Some 7000
  sodium ions pass through each channel during the
  brief period (about 1 millisecond) that it
  remains open.

24
Ion Channels

• Ions moving by facilitated diffusion can traverse
  the plasma membrane through channels created by
  proteins. Ion channel proteins move ions by
  facilitated diffusion.
• Sodium Channels
• Voltage gated sodium channels are crucial for
  the propagation of action potentials in excitable
  membranes. They cause the cell membrane to
  depolarise by allowing the influx of sodium ions
  into the cell.
• Calcium Channels
• Voltage gated calcium channels regulate the
  flow of Ca2 in excitable membranes. for example,
  are found in cardiac, neuronal, endocrine and
  skeletal muscle tissue.
• Potassium Channels
• in excitable membranes, they cause the cell
  membrane to repolarise

25
Aktif Tasima (Aktif Transport)

• Kolaylastirilmis tasimaya benzemekle beraber
  bazi önemli farklar gösterir.Hücre zarindan
  molekül ve iyonlarin karsi tarafa geçisinde
  enerji kullaniliyorsa, bu tür tasimaya aktif
  tasima adi verilir.Aktif tasimada kullanilan
  metabolik enerji ATPnin oksijen kullanilarak
  (aerobik metabolizma) ADPye yikilmasiyla açiga
  çikar. Hücre zari, Endo.ret, Mitokondri
• Isi-pH-Iyonlar-Enzimler- Siyanür- Anestezikler

26

• Active ion pumps
• Moves ions against a concentration gradient
• Requires ATP (Active process)
• Ions are captured and ejected on the other side
  of the membrane

27
Direct Active Transport

• 1. The Na/K ATPase
• The cytosol of animal cells contains a
  concentration of potassium ions (K) as much as
  20 times higher than that in the extracellular
  fluid. Conversely, the extracellular fluid
  contains a concentration of sodium ions (Na) as
  much as 10 times greater than that within the
  cell.
• These concentration gradients are
  established by the active transport of both ions.
  And, in fact, the same transporter, called the
  Na/K ATPase, does both jobs. It uses the energy
  from the hydrolysis of ATP to actively transport
  3 Na ions out of the cell for each 2 K ions
  pumped into the cell.
• This accomplishes several vital functions
• It helps establish a net charge across the plasma
  membrane with the interior of the cell being
  negatively charged with respect to the exterior.
  This resting potential prepares nerve and muscle
  cells for the propagation of action potentials
  leading to nerve impulses and muscle contraction.
  
• The accumulation of sodium ions outside of the
  cell draws water out of the cell and thus enables
  it to maintain osmatic balance (otherwise it
  would swell and burst from the inward diffusion
  of water).
• http//www.brokscole.com/chemistry_d/template/stud
  ent_resources/shared_resource/animations/ion_pump/
  ionpump.html

28

• 2. The H/K ATPase
• The parietal cells of your stomach use this pump
  to secrete gastric juice. These cells transport
  protons (H) from a concentration of about 4 x
  10-8 M within the cell to a concentration of
  about 0.15 M in the gastric juice (giving it a pH
  close to 1). Small wonder that parietal cells are
  stuffed with mitochondria and uses huge amounts
  of energy as they carry out this three-million
  fold concentration of protons.

29

• 3. The Ca2 ATPases
• In resting skeletal muscle, there is a much
  higher concentration of calcium ions (Ca2) in
  the sarcoplasmic reticulum than in the cytosol.
• Activation of the muscle fiber allows some of
  this Ca2 to pass by facilitated diffusion into
  the cytosol where it triggers contraction. After
  contraction, this Ca2 is pumped back into the
  sarcoplasmic reticulum. This is done by a Ca2
  ATPase that uses the energy from each molecule of
  ATP to pump 2 Ca2 ions.

30
(No Transcript)
31
Indirect Active Transport

• Symport Pumps
• The Na/glucose transporter. This transmembrane
  protein allows sodium ions and glucose to enter
  the cell together. The sodium ions flow down
  their concentration gradient while the glucose
  molecules are pumped up theirs. Later the sodium
  is pumped back out of the cell by the Na/K
  ATPase.
• All the amino acids can be actively transported,
  for example out of the kidney tubules and into
  the blood.
• The Na/iodide transporter. This symporter pumps
  iodide ions into the cells of the thyroid gland
  (for the manufacture of thyroxine) and also into
  the cells of the mammary gland (to supply the
  baby's need for iodide).
• Antiport Pumps
• Example Ca2 ions are pumped out of cells by a
  sodium-driven antiport pump

32
Classes of carrier proteins

• Uniport (facilitated diffusion) carriers mediate
  transport of a single solute.
• An example is the GLUT1 glucose carrier.
• The ionophore valinomycin is also a uniport
  carrier.

33

• Example of an antiport carrier
• Adenine nucleotide translocase (ADP/ATP
  exchanger) catalyzes 11 exchange of ADP for ATP
  across the inner mitochondrial membrane.

34
Ion Channels

• Channels cycle between open closed
  conformations.
• When open, a channel provides a continuous
  pathway through the bilayer, allowing flux of
  many ions.
• Gramicidin is an example of a channel.

35

• OSMOS Iki bölüm arasinda suya geçirgen fakat
  kati maddelere geçirgen olmayan bir membran varsa
  ve bölümlerden birinde su derisimi yüksekse,
  yüksek derisimden alçak derisime dogru su
  molekülleri geçerler.Bu olaya osmos denir.Osmos
  deyimi sadece suyun diffüzyonu için
  kullanilir.Bir eriyikteki kati madde derisimi, o
  eriyigin ozmolaritesi olarak bilinir.
• Klasik aritim sistemlerinin yetersiz kaldigi
  sularda (denizsuyu , iletkenligi yüksek olan kuyu
  sulari vb.) uygulanan endüstriyel reverse osmosis
  sistemleri su membranlar üzerinde bulunan 2x10-6
  mm çapindaki gözeneklerden, yüksek basinç altinda
  geçmeye zorlanir. Bu islem esnasinda su
  molekülleri ve bazi inorganik moleküller bu
  gözeneklerden geçebilirken suyun içindeki
  maddelerin çogu bu gözeneklerden geçemez ve
  konsantre su olarak disari atilir.

36

• Osmosis is the net movement of water across a
  selectively permeable membrane driven by a
  difference in solute concentrations on the two
  sides of the membrane. A selectively permiable
  membrane is one that allows unrestricted passage
  of water, but not solute molecules or ions

37

• Two containers of equal volume are separated by a
  membrane that allows free passage of water, but
  totally restricts passage of solute molecules.
  Solution A has 3 molecules of the protein albumin
  (molecular weight 66,000) and Solution B contains
  15 molecules of glucose (molecular weight 180).
  Into which compartment will water flow, or will
  there be no net movement of water?
• Su Solution A dan B ye akarThe size of the solute
  particles does not influence osmosis
• Partikül yogunluguna(sayisina) bagli büyüklügüne
  degil

38
(No Transcript)
39

• In the examples, Solutions A and B are isotonic
  (with each other), Solutions A and B are both
  hypertonic compared to Solution C, and Solution C
  is hypotonic relative to Solutions A and B.

40

• Isotonic - the cells were diluted in serum Note
  the beautiful biconcave shape of the cells as
  they circulate in blood.Hypotonic - the cells in
  serum were diluted in water At 200 milliosmols
  (mOs), the cells are visibly swollen and have
  lost their biconcave shape, and at 100 mOs, most
  have swollen so much that they have ruptured,
  leaving what are called red blood cell ghosts. In
  a hypotonic solution, water rushes into
  cells.Hypertonic - A concentrated solution of
  NaCl was mixed with the cells and serum to
  increase osmolarity At 400 mOs and especially at
  500 mOs, water has flowed out of the cells,
  causing them to collapse and assume the spiky
  appearance you see.
• In blood serum
• Hypotonic
  Isotonic Hypertonic
• 100 mOs 200 mOs 300 mOs
  400 mOs 500 mOs

41
(No Transcript)
42
(No Transcript)
43
(No Transcript)
44
(No Transcript)
45
(No Transcript)
46
(No Transcript)
47
(No Transcript)
48
(No Transcript)
49

• Osmosis the movement of water molecules from an
  area of high concentration to an area of low
  concentration.
• Cell membranes are completely permeable to water,
  therefore, the environment the cell is exposed to
  can have a dramatic effect on the cell.
• Hypertonic Solutions contain a high
  concentration of solute relative to another
  solution (e.g. the cell's cytoplasm). When a cell
  is placed in a hypertonic solution, the water
  diffuses out of the cell, causing the cell to
  shrivel.
• Hypotonic Solutions contain a low concentration
  of solute relative to another solution (e.g. the
  cell's cytoplasm). When a cell is placed in a
  hypotonic solution, the water diffuses into the
  cell, causing the cell to swell and possibly
  explode.
• Isotonic Solutions contain the same
  concentration of solute as an another solution
  (e.g. the cell's cytoplasm). When a cell is
  placed in an isotonic solution, the water
  diffuses into and out of the cell at the same
  rate. The fluid that surrounds the body cells is
  isotonic. http//www.tvdsb.on.ca/westmin/science/s
  bi3a1/Cells/Osmosis.htm
• http//www.stolaf.edu/people/giannini/flashanimat/
  transport/osmosis.swf

50
(No Transcript)
51
OZMOL

• Ozmotik basinç ve ozmotik etkinligin birimine
  denir.Bir ozmol,bir iyonize olmayan molekül
  miktarina esittir.Buna göre 1 mol glikoz eriyigi
  litrede 1 ozmol derisimde glikoz tasir. Bir litre
  suda 180 g glikoz eridiginde 1 ozmollük etkinlik
  olusturur. Bu sivinin osmotik basinci oda
  isisinda 22.4 atmosfer veya 22.4x76017000 mm Hg
  dir.

52

• SÜSPANSIYON Sivi içinde çözünmeyen kati bir
  maddenin parçaciklar halinde dagilmasiyla meydana
  gelen karisima süspansiyon denir.Tebesir tozu ve
  nisasta tanecikleri su içinde adeta asili durumda
  kalirlar,kan hücreleri de ayni sekilde plazma
  içinde bu sekilde dagilirlar.Süspansiyon saydam
  degildir,isigi karsi tarafa geçirmez.Süspansiyonda
  ki bu duruma Tyndall olayi adi verilir.
• EMÜLSIYON Bir sivinin, çözünmedigi baska bir
  sivi içinde küçük damlaciklar halinde dagilmasi
  ile olusan karisima emülsiyon denir.emülsiyon
  bulanik görünümde ve kararsizdir.Zeytinyaginin su
  içinde damlaciklar halinde dagilmasi gibi.
• IMBIBISYON (Içine çekme, kilcal emme) Bazi kati
  maddeler, sivi maddeleri içlerine
  çekerler.Sonuçta kati maddeler içinde bir basinç
  birikimi olusur.Buna imbibition basinci denir.
  (Kontak lenslerde kullanilan polimetilmetakrilat)

53
(No Transcript)
54

• PINOSITOSIS Protein, yag, karbonhidrat, hormon
  ve antikor gibi makro moleküllerin hücre zarina
  sarilarak hücre içine alinmasi olayina
  pinositosiz denir.Alinacak cisim önce hücre
  zarina yapisir.Bu tutunma bölgesinde yüzey
  gerilimi degisir, içe dogru bir kanal meydana
  gelir.Cisimcik pinosom veya pinositik vakuol
  içinde sitoplazma boyunca ilerler.
• FAGOSITOSIS Hücreye alinan madde kati ise
  fagositosis denir.Fagositosis yaslanmis hücre,
  kolloidal partikül ve zararli bakterilerin
  fagosit denilen hücreler ( nötrofil, monosit )
  tarafindan kusatilip hücre içine alinmasi ve
  sindirilmesi anlamina gelir.

55
Phagocytosis

• Phagocytic cells, like macrophages and
  neutrophils, are an early line of defense against
  invading bacteria. However, some bacteria have
  evolved mechanisms to avoid destruction even
  after they have been engulfed by phagocytes.
• Two examples
• Salmonella enterica is a bacterium that causes
  food poisoning in humans. Once engulfed by
  phagocytosis, it secretes a protein that prevents
  the fusion of its phagosome with a lysosome.
• Mycobacteria (e.g., the tubercle bacillus that
  causes tuberculosis) use a different trick.
• When the phagosome is first pinched off from the
  plasma membrane, it is coated with a protein
  called "TACO" (for tryptophan-aspartate-containing
  coat protein).
• This must be removed before the phagosome can
  fuse with a lysosome.
• Mycobacteria taken into a phagosome are able, in
  some way, to keep the TACO coat from being
  removed.
• Thus there is no fusion with lysosomes and the
  mycobacteria can continue to live in this
  protected intracellular location.

56
Pinocytosis

• In pinocytosis ("cell drinking"), the drop
  engulfed is relatively small. Pinocytosis
• occurs in almost all cells
• occurs continuously
• A cell sipping away at the ECF by pinocytosis
  acquires a representative sample of the molecules
  and ions dissolved in the ECF. But pinocytosis
  also provides a much more elegant method for
  cells to pick up critical components of the ECF
  that may be in scant supply.

57
Receptor-Mediated Endocytosis

• Some of the integral membrane proteins that a
  cell displays at its surface are receptors for
  particular components of the extracellular fluid.
  For example, iron is transported in the blood
  complexed to a protein called transferrin. Cells
  have receptors for transferrin on their surface.
  When these receptors encounter a molecule of
  transferrin, they bind tightly to it. The complex
  of transferrin and its receptor is then engulfed
  by endocytosis. Ultimately, the iron is released
  into the cytosol. Receptor-mediated endocytosis
  is many thousand times more efficient than simple
  pinocytosis in enabling the cell to acquire the
  macromolecules it needs.

58

• Another Example the Low-Density Lipoprotein
  (LDL) Receptor
• Cells take up cholesterol by receptor-mediated
  endocytosis. Cholesterol is an essential
  component of all cell membranes. Most cells can,
  as needed, either synthesize cholesterol or
  acquire it from the ECF. Human cells get much of
  their cholesterol from the liver and, if your
  diet is not strictly "100 cholesterol-free", by
  absorption from the intestine.
• The first step in acquiring LDL particles is for
  them to bind to LDL receptors exposed at the cell
  surface. These trans membrane proteins have a
  site that recognizes and binds to the
  apolipoprotein B-100 on the surface of the LDL.
  The portion of the plasma membrane with bound LDL
  is internalized by endocytosis. A drop in the pH
  (from 7 to 5) causes the LDL to separate from
  its receptor. The vesicle then pinches apart into
  two smaller vesicles one containing free LDLs
  the other containing now-empty receptors. The
  vesicle with the LDLs fuses with a lysosome to
  form a secondary lysosome. The enzymes of the
  lysosome then release free cholesterol into the
  cytosol. The vesicle with unoccupied receptors
  returns to and fuses with the plasma membrane,
  turning inside out as it does so (exocytosis). In
  this way the LDL receptors are returned to the
  cell surface for reuse.

59
(No Transcript)
60
Parasites

• They have evolved (evrim) surface molecules that
  serve as decoy (tuzak) ligands for receptors on
  the target cell surface. Binding to these
  receptors tricks the cell into engulfing the
  parasite.
• Some examples
• Influenza virus. The hemagglutinin on the surface
  of the virus binds to carbohydrate on the surface
  of the target cell tricking the cell into
  engulfing it.
• Listeria monocytogenes. This food-borne bacterium
  can be dangerous to people with defective immune
  systems as well as to pregnant women and their
  newborn babies. It has two kinds of surface
  molecules each a ligand for a different receptor
  on the target cell surface.