Physiology Introduction (for pharmacists).pptx

As a basic medical science, physiology is taught as a prerequirement of pharmacology course, for pharma students.
A concise explanation of body homeostasis control theory, interaction of our body with external and internal environment different components. external environment components like stress, fear, food, chemicals, and microorganisms; internal environment composes body fluids, electrolytes, blood PH, and body temperature.
How the body maintain normal body functions and variables within the normal range during dealing with its environment.
how different molecules distribute in different body fluids compartments, according to their physiochemical properties.
cell membrane composition. cell membrane proteins and their function.
transmembrane proteins types and role. Transporting membrane proteins. Receptor membrane proteins. second messengers and mediators.
intercellular communication and chemical messengers or mediators.

1. Physiology Introduction By Suad Zuhair B. Pharm, M . Pharm.  Clin .  Pharmco .                       

2. Physiology: the science which analyses the body functions and their interaction with internal and external environment.  By Suad Zuhair B. Pharm, M. Pharm

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4. (I) Homeostasis All the automatic reactions which take place in the body in response to changes in the external or internal environments, which tend to adjust and correct all deviations from normal.  By Suad Zuhair B. Pharm, M. Pharm

5. External environment: psycho-social (e.g. Stress), physical (heat, light, sound, motion and radiation), chemical (food, water, O2, CO2, drugs), biological (microorganisms and parasites) Internal environment : physical and chemical properties of extracellular body fluid: water content, electrolytes , blood PH (7.35 – 7.45), and temperature (36.1- 37.2). By Suad Zuhair B. Pharm, M. Pharm

6. Control theory (How to maintain homeostasis) Detectors and sensory receptors all over the body sent signals to the body control system ( nervous and endocrine systems), which in turn initiate corrective feedback processes. By Suad Zuhair B. Pharm, M. Pharm

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8. Adjusting homeostasis Short-term corrections of body variables. When the weather is hot, our body increases the skin blood flow near the surface of the body and dilate the blood vessels to allow heat loss. The reverse occurs with cold weather . External environment change When the body is dehydrated (water loss), a feedback mechanism lead us to feel thirsty and ADH is released. Internal environment change By Suad Zuhair B. Pharm, M. Pharm

9. Adaptive homeostasis Long-term adjustments of body variables. people living in cold environment increase their thyroid function  to generate heat from a higher rate of metabolism. External environment change heart remodelling after cardiac tissue damage. Internal environment change   By Suad Zuhair B. Pharm, M. Pharm

10. If the body fails to adjust or adapt changes disease will occur By Suad Zuhair B. Pharm, M. Pharm

11. Body fluids 60% of human body is made of water (82% in newborns and 52% in elderly). For a man with 65 kg body weight, it contain about 40 litters of water found in different compartments as follow: By Suad Zuhair B. Pharm, M. Pharm

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13. Molecules distribution in different fluid compartments: By Suad Zuhair B. Pharm, M. Pharm

14. Tissue fluid exchange Fluid exchange between blood compartment (capillary blood) and the interstitial compartment takes place continuously, to renew tissue fluids, to supply needed materials, and to remove cells metabolic products. It depends on two forces: Hydrostatic pressure (fluid pressure due to heart contraction) filtration. Equal to 35 mmHg at the arteriolar end and 18 mmHg at the venous end Osmotic pressure (due to plasma protein concentration) absorption. Equal to 25 mmHg through all of the capillary bed By Suad Zuhair B. Pharm, M. Pharm

15. Filtration: fluids pass to outside of the capillaries taking oxygen, amino acids and glucose. Absorption: fluids pass to inside of capillaries removing CO2 and byproducts. By Suad Zuhair B. Pharm, M. Pharm

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17. Body fluids electrolytes Plasma Interstitial fluid Intracellular fluid Cations ( mmol /l) Na + 145 140 10 K + 4 4 145 Ca ++ 5 5 1 Mg ++ 2 2 40 Total ( + ) 156 151 196 Anions ( mmol /l) Cl ¯ 105 110 3 HCO3 ¯ 28 31 10 Protein 17 4 45 HPO 4¯ 6 6 138 Total (-) 156 151 196 By Suad Zuhair B. Pharm, M. Pharm

18. (II) The cell membrane The body structural and functional units : Organ systems: nervous, cardiovascular, renal, endocrine, digestive, respiratory, reproductive systems.. organs: brain, heart, kidneys, stomach, lungs, liver.. Tissues ( only 4 types ): nervous tissue, muscular tissue, connective tissue, epithelial tissue. Cells ( the basic structural and functional unit of the living organism ): stem cells, sensory cells, secretory cells, nerve cells, endothelial cells, ion-transporting cells, contracting cells, antigen-presenting cells, phagocytic cells, killing cells, supporting cells. By Suad Zuhair B. Pharm, M. Pharm

19. Cell membrane : a semi-permeable phospholipid bilayer. Bilayer: the hydrophilic head (phosphate ends) faces the water of the ECF and cytoplasm, while the hydrophobic tail (lipid) of the two layers faces each others inside the membrane. Semi-permeable: some molecules can diffuse across the lipid bilayer but others cannot: Non- polar molecules and some small polar molecules (e.g. water and ethanol) can simply diffuse through lipid bilayer . Polar (e.g. sugar, amino acids) and highly charged (e.g. ions) molecules can only pass through specialized protein molecules embedded in the lipid bilayer. By Suad Zuhair B. Pharm, M. Pharm

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21. Membrane proteins : Peripheral proteins (extrinsic); loosely bound to one surface of the cell membrane. Exterior e.g. antigens Interior e.g. cell enzymes (b) Integral proteins (intrinsic); closely bound to one surface or extend across the hole lipid bilayer ( transmembrane proteins ). By Suad Zuhair B. Pharm, M. Pharm

22. Transmembrane proteins : They are integral membrane proteins which extend across the hole lipid bilayer: (1) transporter proteins, (2) receptor proteins, (3) enzyme proteins, (4) anchor proteins. By Suad Zuhair B. Pharm, M. Pharm

23. Transporter proteins They are transmembrane proteins act as translocators of ions or molecules across the cell membrane. They are two types: ( 1)Channel proteins : a. Non-gated channels: still open all time transporting ions and molecules down their concentration gradient. Examples water aquaporins ; sodium and chloride ion channel proteins in kidney tubules. b . Gated channels : opening and closing regulated by chemical messengers “ chemical or ligand- gated ”, by change in the membrane potential “ voltage-gated”, or by stretching/pressure “ mechanically-gated ” to transport ions down their concentration gradient. Examples nicotinic receptors, voltage-gated sodium channels in nerves and muscles, baroreceptors. By Suad Zuhair B. Pharm, M. Pharm

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25. (2) Carrier proteins : by undergoing reversible conformational changes the bound molecule move from one side of the cell to another . They are two types: a. Concentration-driven carrier proteins : transporting ions or molecules down t heir concentration gradient. b. Energy-driven carrier proteins : transporting ions or molecules against their concentration gradient, using two types of driving energy: i . Coupled carriers or ion-driven (co-transport): couple the transport against conc. gradient of one molecule to the transport down conc. Gradient of another one, either in the same direction ( semiport ) or in the opposite direction ( antiport ). Example sodium-glucose cotransporter in kidney. ii. ATP-driven pumps : hydrolysis ATP as a source of energy for transport against the conc. gradient. Example Na+/k+ ATPase pump in excitable tissues cells. By Suad Zuhair B. Pharm, M. Pharm

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27. So membrane transportation is either: Simple diffusion transport : it is the diffusion of a substance (lipophilic) across the lipid bilayer down its concentration gradient. Facilitated diffusion transport : it is the diffusion of a substance (hydrophilic) across specialized membrane proteins down its concentration gradient. Active transport : the transport of a substance (hydrophilic) across specialized membrane proteins against its concentration gradient by energy use. By Suad Zuhair B. Pharm, M. Pharm

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29. Receptor proteins They are transmembrane protein molecules, act as signal transducers , with extracellular domain which include signal (chemical substance) binding site and intracellular domain activates intracellular signal cascade after signal binding. Their numbers are not fixed, can increase (up-regulation) or decrease (down-regulation). There are three categories of membrane or surface receptors: ( 1) Channel-linked receptors (ligand-gated ion channels) (2) Enzyme-linked or Catalytic receptors (or protein-kinase receptors) (3) G-protein linked receptors (7-transmembrane or metabotropic receptors) By Suad Zuhair B. Pharm, M. Pharm

30. They either act directly by changing intracellular ionic concentration (electrochemical gradient) or through generation of a second messenger (intracellular mediator). By Suad Zuhair B. Pharm, M. Pharm

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32. (1) Ion c hannel-linked receptors Interaction of the chemical signal with the binding site of the receptor causes the opening or closing of an ion channel  in another part of the same molecule. The resulting ion flux , changes the membrane potential of the target cell, and results in cellular response. Example; neurotransmitter receptors such as nicotinic receptors. By Suad Zuhair B. Pharm, M. Pharm

33. (2) Enzyme-linked receptors: The intracellular domain is an enzyme (most of them are protein kinases) whose catalytic activity is regulated by the binding of an extracellular signal. The catalyzed protein (active form) will results in cellular response. Example; growth factor receptors. By Suad Zuhair B. Pharm, M. Pharm

34. (3) G-protein coupled receptors: GPCRs are the largest family of membrane receptors. Consist of a single polypeptide chain that spans through the cell membrane in a zigzag form seven times so also called “ 7-transmembrane receptors ”. The amino-terminal on the extracellular side and the carboxy -terminal on the intracellular side. The coupled G protein is composed of three main subunits: alpha (α), beta (β), and gamma (γ). The Gα subunit is bound to GDP. Binding of a ligand to the GPCR results in G α subunit activation with the exchange of GDP to GTP and dissociation from the Gβγ dimer and from the receptor . By Suad Zuhair B. Pharm, M. Pharm

35. The two subunits start signal transduction cascades using different second messengers (or intracellular mediators) , which will results in cellular response . The most common second messengers are cAMP , Ca ++ , and IP3 . T he G α subunit have three subtypes: 1. The G α s subtype stimulates the membrane enzyme adenylyl cyclase (AC) which converts ATP to cyclic AMP. So increases cAMP levels. 2. The G α i subtype inhibits AC and decreases cAMP levels. 3. The G α q family members activate a membrane enzyme, phospholipase C (PLC), resulting in hydrolysis of a membrane phospholipid, phosphatidylinositol bisphosphate (PIP2) into diacylglycerol and inositol triphosphate (IP3 ). Examples; adrenergic receptors, muscarinic receptors… By Suad Zuhair B. Pharm, M. Pharm

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37. Intracellular receptors For lipid-soluble ligands which can pass through the cell membrane. They either found in the cytoplasm or on the nucleus. They act on nuclear DNA to stimulate transcription of messenger RNA for protein synthesis. This proteins results in different cellular responses. Examples; steroid receptors and thyroid receptors. By Suad Zuhair B. Pharm, M. Pharm

38. (III) Intercellular communication Communication between cells takes place mostly indirectly by “ chemical messengers ( or chemical mediators )” or directly through Gap junctions. There are three main types of chemical messengers: (1) chemical transmitters (neurotransmitters), released by nerve cells. (2) hormones, released by endocrine cells. (3) paracrine hormones, released to act locally on neighboring cells. Chemical messengers act through membrane receptors or intracellular receptors. By Suad Zuhair B. Pharm, M. Pharm

39. Gap junctions are intercellular channels that permit direct cell–cell transfer of ions and small molecules. By Suad Zuhair B. Pharm, M. Pharm

40. The End By Suad Zuhair B. Pharm, M. Pharm