Chapter 1: Cell Physiology PDF

# Chapter (1) CELL PHYSIOLOGY - Cell structure and functions - Body fluid compartments and composition - External and internal environment - Effect of changes in temperature, pH, and osmotic pressure on cell activity ## The cell - The cell is the basic structural and functional unit of organisms....

# Chapter (1) CELL PHYSIOLOGY - Cell structure and functions - Body fluid compartments and composition - External and internal environment - Effect of changes in temperature, pH, and osmotic pressure on cell activity ## The cell - The cell is the basic structural and functional unit of organisms. - It is the simplest unit of the biological structure into which an organism can be divided and still retain the characteristics we associate with life. - In unicellular organisms, all vital processes occur in a single cell. - In multicellular organisms, various cell groups have taken over particular functions. - The study of mammalian physiology involves the dynamic interrelationship among various molecules (molecular level), organelles (subcellular level), cells (e.g. muscle cells, cellular level), tissues (e.g. muscle tissue, tissue level), organs (e.g. the heart, organ level), systems (e.g. cardiovascular system, system level) and reaches ultimately to the level of the organism as a whole. - Cells vary greatly in their size and shape according to their functions. - No single cell can be referred to as the "typical cell" of the body, but there are features common to all cells for maintenance of each cell's life. ## Cell Structure and Function ### **Chemical Structure (chemical composition) of a cell** - **Intracellular fluid (ICF)** 1. Water (70-80%) which acts as a medium for chemical reactions and transport of substances. 2. Electrolytes: - **cations:** K+, Na+, Mg++ - **anions:** HCO3-, PO4-, Cl- 3. Proteins (10-20%) 4. Lipids 5. Carbohydrates (10%) ### **Physical Structure** - **Organelles** - are the living specialized structural parts of cytoplasm and nucleus. - Organelles can be either membranous or nonmembranous. - **Cytoplasmic membranous organelles:** cell membrane, endoplasmic reticulum, mitochondria, Golgi apparatus, lysosomes, and peroxisomes - **Cytoplasmic non-membranous organelles:** ribosomes, centrioles, vaults, and microtubules and microfilaments. - **Nuclear membranous organelle:** nuclear membrane or envelope - **Nuclear non-membranous organelles:** chromatin and nucleolus - **Inclusion bodies** (nonliving) temporary components of cytoplasm viz. lipid globules, glycogen granules, secretory granules. ## Cytoplasmic Membranous Organelles ### Cell Membrane - The membrane surrounding the cell and the membranes of other organelles have many features in common (plasma membrane, unit membrane). ### Structure - The cell membrane is a dynamic, nonrigid semipermeable structure about 7.5 to 10 nm (nanometres) thick and composed primarily of protein and lipids (phospholipids and cholesterol). Basically, proteins are embedded in a lipid bilayer. - The shape of the phospholipid molecule is roughly that of a clothespin. - **head** (phosphate portion, polar, hydrophilic) - **tails** (nonpolar hydrophobic fatty acid chains) - They exist as a bimolecular layer with the hydrophilic (water soluble) heads (phosphate portion ) facing (1) the aqueous medium that bathes exterior of the cells, and (2) the aqueous cytoplasm; the hydrophobic fatty acid chains (the tails) face each other in the middle of the membrane. This arrangement imparts fluidity to the lipid bilayer. - Substances which are not lipid soluble have difficulty passing through the hydrophobic interior. This contributes towards selective permeability of the cell membrane. - Globular proteins are embedded in a fluid phospholipid bilayer matrix. The constituents of the membrane are constantly renewed (dynamic) and the proteins of various shapes and sizes (forming a mosaic) float in the lipid sea. Some proteins change shape and move laterally in the membrane (dynamic). This is called "dynamic fluid mosaic model" of cell membrane structure. ### Types of Proteins in the Cell Membrane 1. **Integral Proteins:** - They are embedded in the membrane. - They may exist as separate globular units and many pass through or embedded in one leaflet of the membrane and are integral components of the membrane. - Many of them have specific functions (e.g. as transport proteins; contribute towards selective permeability of the cell membrane.) 2. **Peripheral Proteins:** - They stud the inside and outside of the membranes and are weakly bound to the hydrophilic regions of specific integral proteins. - **Peripheral proteins held by glycosylphosphatidylinositol (GPI) anchors include enzymes such as alkaline phosphatase, various antigens, and a number of cell adhesion molecules (CAMs).** ## Functions of Cell Membranes 1. By forming a closed compartment around the cell, it allows cell individuality and maintains cell integrity. 2. **Transport of substances into and out of the cell:** This is governed by the selective permeability of the cell membrane. - **Integral (transmembrane proteins)** - **Some proteins in the cell membrane function as "transport proteins" acting as** - **Channels:** through which specific ions diffuse. - Some channels are continuously open. - Some channels are "gated" i.e., they can be opened or closed by - changes in the electrical potential (voltage) across the cell membrane (voltage-gated channels) - binding of chemicals (ligands) such as hormones or neurotransmitters (ligand or chemically-gated channels) - binding of chemicals (intracellular signaling molecules) such as cAMP or (IP3) (second messenger gated channels) - other stimuli such as mechanical stretch (mechanically-gated channels). - **Carriers:** they bind to the substances and translocate them from one side of the membrane to the other side. - Carriers moving the substances along their concentration gradient facilitate diffusion of these substances. - **Pumps:** these are carriers that move the substances against their concentration gradient. - They have adenosine triphosphatase (ATPase) activity and use the energy liberated from hydrolysis of ATP for the uphill transport. - **e.g. sodium-potassium pump for active transport of these ions across the membrane.** - **Transport proteins (carriers or pumps) may also be classified in a functional sense according to the number of substances moved and the direction of movement:** - **A uniport transports only one substance (direction depends on the gradient) e.g. glucose transporter (GLUT) in muscle cells facilitates glucose diffusion by moving glucose into the cells.** - **Cotransporters simultaneously transport more than one substance.** - **A symport moves two or more different substances in the same direction.** - e.g. Sodium dependent glucose transporter (SGLT) in intestinal mucosal and renal tubular cells moves both glucose and Nat into the cells. - **An antiport (countertransporter) moves two or more different substances in the opposite directions.** - e.g. - Na+-Ca²+ antiport moves 3Na into and Ca²+ out of cardiac muscle cells - Band 3 protein (anion exchanger) in RBCs and acid-secreting cells of stomach moves HCO3- and Cl in opposite directions along their concentration gradients. - Na - K+ pump moves Na+ and K+ in opposite directions against their concentration gradients. 3. **Other proteins in the cell membrane function as** - **receptors**, which provide binding sites for many molecules e.g., hormones and drugs, with great specificity and affinity. - **enzymes**, catalyzing reactions at the surfaces of the membrane. - **antigens**, carrying immunological identification marks e.g., blood group antigens, transplant antigens. - **Cell Adhesion Molecules (CAMs)**: These molecules attach cells to each other and to the basal lamina, forming intercellular connections which give strength and stability to tissues. - Many CAMs pass through the cell membrane and are anchored to the cytoskeleton. - Others bind to large molecules in the extracellular matrix. - CAMs can be divided into four broad families: integrins, adhesion molecules of the Ig G superfamily of immuno-globulins, cadherins, and selectins. - They play an important role in - development and formation of nervous system and other tissues - holding tissues together (by CAMS called cadherins) - inflammation (e.g. adhesion of neutrophils to endothelial cells, and of platelets to extracellular matric, macrophage activity, binding of immunoglobulins) - wound healing and scar formation (adhesion of fibroblasts, epithelial cells) - spread of tumors (metastasis of cancer cells) - transmission of signals into and out of the cell (e.g. integrins in contact with extracellular matric and integrins in contact with cytoskeleton). 4. **The cell membrane exhibits endocytosis (pinocytosis, phagocytosis) and exocytosis (emeiocytosis), transporting particulate matter and proteins into or out of the cells.** ## Intercellular Connections - Two types of junctions form between cells that make up tissues. - The junctions that tie cells together giving strength and stability to tissues: - **Tight junction (zonula occludens):** are made up of protein ridges, half from one cell and half from the adjacent cell. There are three main families of transmembrane proteins that contribute to tight junctions: occludin, junctional adhesion molecules (JAMs) and claudins; and several more proteins that interact with cytosolic side. They are found in apical margins of epithelial cells in the intestinal mucosa, renal tubules and the choroid plexus. Tight junctions permit the passage of some ions and solutes between adjacent cells (paracellular pathway), and the degree of this leakiness varies. Tight junctions also prevent the movement of proteins in the plane of the membrane, helping to maintain the different distribution of transporters and channels in the apical and basolateral cell membranes that transport across epithelial cells. - **Desmosomes:** spot-like patches characterized by apposed thickening of the membranes of two adjacent cells - **Hemidesmosomes:** half desmosomes that attach cells to an underlying basal lamina. - **Zonula adherens:** a continuous structure on the basal side of the zonula occludens and is a major site of attachment for intracellular actin fibers. - **Gap Junctions:** that permit transfer of ions and molecules from one cell to another. - The hexagonal arrays of protein units called connexons in the membrane of each cell line up with each other forming a single channel bridging the membranes of two cells. - They permit substances such as ions, sugars, and amino acids to pass between the cells without entering the ECF, enabling the rapid propagation of electrical activity from cell to cell and the exchange of chemical substances. Such junctions are found in cardiac and smooth muscles, and form the physical basis of "functional syncytium". - **cells work together e.g. heart, urinary bladder organs** ## Cytoplasmic Non-membranous Organelles ### Ribosomes - Ribosomes are granules composed of 2 subunits, the larger 60s and smaller 40s subunits. The ribosomes are the site (work bench) of protein synthesis. They contain about 65% RNA (ribonucleic acid) and 35% protein. - **Free ribosomes in the cytoplasm synthesize proteins utilized in the cell e.g. haemoglobin and the proteins found in mitochondria.** ### Centrioles (Centrosomes) - Centrioles are a pair of short cylinder-like structures located between the Golgi complex and nucleus. They are at right angles to each other. The wall is made up of microtubules. - **Functions** - Centrioles are concerned with the movement of the chromosomes during cell division by forming the poles of the mitotic spindle. ### Microtubules and Microfilaments - **Microtubules** are long and hollow structures about 15 nm in diameter. - **Microfilaments** are long solid fibers 4-6 nm in diameter. ### **Functions** 1. **Microtubules** (made up of globular protein subunits called tubulin) provide tracks along which substances such as secretory granules are moved from one part of the cell to another ("intracellular traffic", e.g. axoplasmic transport in nerve cells) and the protein molecules with ATPase activity that move various substances along microtubules are called molecular motors. Microtubule-based molecular motors include kinesin and dynein. Microtubules also form the mitotic spindle, which moves the chromosomes in mitosis. 2. Microtubules, microfilaments, and proteins that tie them together form the skeleton of the cell. - The cytoskeleton not only maintains cell shape, but also permits it to change shape and move. 3. **Microfilaments** are made up of actin. All cells contain actin and a variety of actin-binding proteins, including myosin (an actin-based molecular motor.) - They play a role in muscle contraction (as myofilaments), movement of microvilli in the intestinal mucosa, cell movement (abundant in pseudopodia) and clot retraction. - Filaments with diameters intermediate between the microtubules and microfilaments connect the nuclear membrane to the cell membrane. - They also help the cell to resist external pressure. - The cells rupture more easily and skin blisters are common when these filaments (called intermediate filaments) are absent or abnormal. ### Vaults - Vaults are hollow, octagonal structures that are the same shape and size as the nuclear pores. - They are believed to be cellular trucks that dock at the nuclear pores and pick up cargo for transport from the nucleus. - Vaults may transport mRNA or the ribosomal subunits from the nucleus to the cytoplasmic sites of protein synthesis. ## Nucleus - A nucleus, an information centre, is present in all animal cells that divide: - **Nuclear membranous organelles: Nuclear membrane or envelope** - Nuclear membrane is a double unit membrane, 25-40 nm thick, enclosing the space called the perinuclear cistern. - The pores in the nuclear membrane are closed by a thin membrane. - The membrane permits passage of molecules as large as RNA. - **Nuclear non-membranous organelles : Chromatin** - Chromatin granules are dark densely stained particles which condense to form chromosomes during cell division. - Chromosomes are made up of DNA and the basic protein called histone. - The chromosomes carry the genetic message; the complete blueprint for all the heritable characteristics of the cell. - The functional unit of DNA is a gene which represents the amount of genetic information required to form one polypeptide or protein molecule. The proteins formed include all the enzymes, and these in turn control the metabolism of the cell. - **Human cells contain 46 chromosomes: 22 pairs of somatic chromosomes (autosomes) and 2 sex chromosomes - X and Y in males and two X chromosomes in females. - This number is the diploid number. Germ cells (spermatozoa and ova), on the other hand, contain 23 chromosomes: 22 autosomes and one sex chromosome. This number is the haploid number.** - In humans, one copy of the entire double-stranded DNA content is referred to as haploid genome and consists of approximately 3 x 10⁹ base pairs in 23 separate molecules, each part of a different chromosome. - **Nucleolus** - A nucleolus is a patch-work of granules with no limiting membrane. The granules are rich in ribonucleic acid (RNA). - It functions as the site of ribosomal RNA synthesis and for temporary storage of messenger ribonucleic acid (mRNA). ## DNA (Deoxyribonucleic acid) - The DNA molecule is a double helix formed by 2 chains of polydeoxyribonucleotides held together by hydrogen bonds. - Deoxyribonucleotide is made up of a phosphoric acid, a pentose sugar (deoxyribose) and a nitrogenous base (purines: adenine, guanine; pyrimidines: thymine, cytosine). - Adenine (A) always pairs with thymine (T). - Guanine (G) always pairs with cytosine (C). - The sum of purines equals the sum of pyrimidines. - The 2 chains are complementary (with regards to base pairing) and antiparallel (oriented in opposite directions). - Each chain is made up of deoxyribonucleotide units linked by 3', 5' phosphodiester bonds. - The genetic message is coded by the sequence of the bases in deoxyribonucleotide chains. - The message is transferred to the sites of protein synthesis in the cytoplasm by RNA. - The text of the message is the order in which the amino acids are lined up in the proteins synthesized. ## Functions of DNA - DNA is the carrier of genetic information. The genetic information is expressed in terms of protein synthesis (Gene expression) (gene of form - The strands of DNA serve as template for its own synthesis (replication) and for formation of RNA. - It is worth noting that DNA is responsible for the maintenance of the species; it passes from generation to the next in germ cells. - RNA, on the other hand, is responsible for the production of the individual; it transcribes the information coded in the DNA and forms a mortal individual. ## RNA (Ribonucleic acid) - RNA molecule is a single strand of ribonucleotides, each of which is made up of a phosphoric acid, a pentose sugar (ribose) and a nitrogenous base (purines: adenine, guanine; pyrimidines: cytosine, uracil). - Ribonucleic acids exist mainly in the cytoplasm. There are 3 types of RNA: 1. **Ribosomal RNA (rRNA)** - Found in ribosomes. - Ribosomal RNA makes up 65% of the ribosome mass, the rest being protein. - Ribosomal RNA is involved in translation of genetic message. 2. **Transfer RNA (tRNA) (Soluble or Acceptor RNA)** - There are at least 20 tRNA molecules in every cell, at least one corresponding to each of the 20 amino acids required for protein synthesis. - The RNA chain is arranged in a clover leaf structure. - The tRNA molecules carry activated specific amino acids required to the sites of protein synthesis and serve as adaptors for the translation of the information in the nucleotide sequence of the mRNA into specific amino acids. 3. **Messenger RNA (mRNA)** - Messenger RNA is a single stranded molecule and complementary to the sense strand of the DNA. - Messenger RNA functions as messenger conveying the genetic information from the nucleus to the protein-synthesizing machinery where it serves as a template on which a specific sequence of amino-acids is polymerized to form a specific protein. ## Protein Synthesis ### The Genetic Code - Genetic information lies in the linear sequence of nucleotides in DNA and is transcribed from the DNA into mRNA before protein is synthesized. - In the nucleotide sequence of the mRNA molecule, code words exist for each amino acid. - Each code word, termed a codon, consists of a triplet of non-overlapping bases derived from 4 different nucleotides (A, C, G and U) present in the mRNA. - Thus, there are 64 (4³) possible codons. - Amino acids have been assigned to 61 of the codons, and the other 3 are signals to terminate the synthesis of the peptide chain. - Since there are only 20 amino acids, it is clear that more than one codon codes for a given amino acid. - e.g. both codons UUU and UUC stand for the amino acid phenylalanine. ### The process of protein synthesis The biosynthesis of protein occurs in 4 main stages: 1. Transcription (DNA → mRNA) 2. Post-transcriptional modification 3. Translation (tRNA) 4. Post-translational modification 1. **Transcription** - Transcription is the formation of mRNA on the template of a strand of DNA (the sense strand). - The process is catalyzed by DNA-dependent RNA polymerase. - The mRNA so synthesised is called the pre - mRNA or heterogenous nuclear RNA (hn RNA). 2. **Post-transcriptional modification** - The RNA synthesised is processed before it is released into the cytoplasm. - The mRNA thus formed is called the definitive mRNA. 3. **Translation** - On the ribosomes the information carried by the mRNA is translated from the linear sequence of codons on the mRNA into protein. - The tRNA molecules, each loaded with its specific amino acid, serve as adaptors for assembling amino acids in the correct sequence along the mRNA molecule. 4. **Post-translational modification** - After the polypeptide chain is formed, it is modified by one or more chemical reactions to the final protein. - This process is responsible for generation of functional molecules, e.g., formation of the hormone insulin from proinsulin. ## Normal Values - Individuals vary, and so does normalcy. - Also, homeostatic mechanisms are not cent per cent efficient. - Thus, the outputs of these systems oscillate within certain limits. - Thus, it is not scientific to say "the normal heart rate is 72 beats/min." - It is more appropriate to give a range ("the normal heart rate of an adult at rest is 60 to 90 beats/min"). ## Total Body Water (TBW) and Body Fluid Compartments - The chief constituent of living tissue is water. - The percentage of water varies with sex, age, and lean body mass, as evident from tables 1.1 & 1.2. ### Table 1.1: Approximate composition of the body. | | Normal adult man | Normal adult woman | |---------------|--------------------|---------------------| | Water (%) | 65 - 70 | 55 - 60 | | Fat (%) | 5 | 18 | | Lean (fat free) body mass | 25 | 22 | | *eg bone, muscle* | | | ### Table 1.2: Percent total body water (TBW) - Infants have a large TBW; most of which is intracellular; this makes them very vulnerable to dehydration | | Infant | Male | Female | |---------|-------|--------|--------| | Thin | 80 | 65 | 55 | | Average | 70 | 60 | 50 | | Fat | 65 | 55 | 45 | ### Note: - infant = < 1 year - TBW: - infant > adult - male > female - thin > fat ## Entry / Exit - The ECF communicates with the outside world through four exit routes (skin, lungs, gut, and urinary tracts) but the only natural entry to it is through the mouth and gut. - Losses through the skin and lungs are influenced by changes in external factors which cannot be controlled. - Thus men climbing high mountains in cold, dry air will have enormous water losses from the lungs as hypoxia demands increased ventilation; men suddenly transported to a tropical climate may sweat unmanageably. - Intestinal losses are not "physiological" and are related to abnormal states where vomiting or diarrhoea occurs. - Only the losses from the kidney can be regulated precisely; this organ thus plays a crucial role in the regulation of the ECF volume. ## The Fluid Compartments - The ECF is distributed in two compartments viz. INTERSTITIAL FLUID (ISF) which surrounds the cells and INTRAVASCULAR FLUID (IVF) (Plasma). The intracellular fluid (ICF) compartment is twice as large as the ECF compartment (see Fig. 1.1). - The relative volumes and composition may be summarised as follows :- ### **Table 1.3: Some features of different fluid compartments.** | | % body weight | Major cation | Major anion | Osmolality (mosm/kg) | PH | |------------|---------------|--------------|-------------|-----------------------|-----| | TBW | 60 | | | | | | ICF | 40 | K+ | PO4-, Prot | 290±5 | 7.3 | | ECF: ISF | 15 | Na+ | Cl- | 290±5 | 7.4 | | ECF: IVF | 5 | Na+ | Cl- | 290±5 | 7.4 | ## Dissolved in water - Dissolved in water (which is the solvent in biological systems) are the following solutes:- - **crystalloids** e.g. glucose, sucrose - **colloids** e.g. plasma protein - **electrolytes** e.g. sodium, potassium - Some solutes are easily dissolvable whilst others must be protein-bound to become soluble e.g. iron, copper, and some hormones like cortisol and thyroxine. ## Man and His Environment ### The External Environment - The environment in which organisms (including man) exists may be termed the external environment: it may be - **physical environment** (e.g. air temperature, humidity, light, noise, radiation) - **chemical environment** (e.g. chemicals in air and water, dyes, drugs) - **biological environment** (e.g. plants, animals, microorganisms like bacteria and viruses, parasites) - **social environment** (e.g. family, friends, foes, human relations) - The external environment is variable and is always changing. - (DYNAMIC) - **relatively constant** - **absolutely constant** - **compared to external environment** ### The Internal Environment - The cells of our body are not in direct contact with the external environment but exist in an "internal sea " of body fluids (fluid = water + dissolved substances). - Thus the fluid surrounding the cells (the extracellular fluid) is the environment with which the body cells are in actual contact. - This fluid environment of the cells, because it exists inside our body, is called the internal environment. - The fluid in the body is distributed in the cells (the intracellular fluid, ICF) and outside the cells (the extracellular fluid, ECF). - The internal environment consists of two fluid types: - **intravascular fluid (IVF):** Part of the extracellular fluid that fills the vascular system (blood and lymph vessels) is called intravascular fluid (IVF). Fluid that fills the blood vessels is called blood plasma and it forms the environment of the blood cells. - **interstitial fluid (ISF or tissue fluid):** Part of the extracellular fluid outside the vascular system, surrounding (bathing) the cells is called interstitial fluid (ISF or tissue fluid) and forms the environment of the tissue cells. - Thus, the ECF constitutes the internal environment. Its composition and volume are precisely regulated even in the face of widely varying external conditions. This environment is like a "shell" of fluid which enables the cells to withstand changes in the outside world. ## Units For Measuring Solute Concentration - Concentration of solutes are used to be expressed by weight (g% or g/dL), or by arbitrary terms such as "normal saline" (0.9% NaCl). However, these give no information about the interactions between substances. - With the introduction of SI Units, substances with known molecular weights are now expressed as moles, equivalents or osmoles. - When the molecular weight is not known or if there is a mixture of substances, g/l is still in use. ### 1. Moles - Mole = g/molecular weight of a substance - mmol = 1/1,000 mole - μmol = 1/1,000,000 mole - e.g. 1 mole of NaCl = 23 + 35.5 g = 58.5 g - 1 mmol of NaCl = 58.5 mg - 1 mole of glucose (C6H12O6) = (12 x 6) + (1 x 12) + (16 x 6) = 180 g ### 2. Equivalents - 1 Equivalent = mol/valency and - 1 mEq = mmol/valency - NaCl = (1 Eq Na*) + (1 Eq Cl-) - 1 Eq of Na* = 23/1 = 23 g - 1 Eq of Ca** = 40/2 = 20 g - N.B. Values for mmol and mEq are the same for monovalent ions. ### 3. Osmoles - 1 osml = molecular weight of substance in grams/ number of freely moving particles each molecule liberate in solution - 1 mosmol = 1/1000 osmole/molecular wt in mg - Osmolar concentration may be measured by the depression of freezing point (DFP). - If the solution depresses freezing point by 1.86°C, its concentration is 1 mol/l (1000 mmol/l). - If DFP is 1.86°C, concentration is 1 mol/l (1000 mmol/l) or 1 osmol/l (1000 mosmol/l). - If DFP is X, concentration is X/1.86 osmol or X / 0.00186 mosmol. - The osmolarity of a solution is the concentration of osmotically active particles, expressed as the osmoles or milliosmoles per liter of solution (osm/l or mosm / L), whereas osmolality is the concentration of osmotically active particles, expressed as the osmoles or milliosmoles per kg of solvent (osm/kg of water or mosm / kg of water). - Osmolarity is affected by the volume of various solutes as well as the temperature, but osmolality is not. - Since water is the solvent in biological system and its density is 1, osmolar concentrations can be expressed as osm/l of water. - Normal plasma osmolality: 290 ± 5 mosm / kg or mosm / I (Sl unit) ### 4. pH - The concentration of H+ ions in the body fluids is very low (4 x 10⁻⁸ mol/l or 40 nanomoles/l = pH 7.4) so it is expressed in terms of pH which is the negative logarithm of the H+ concentration. - Thus, a difference of 1 pH unit reflects a tenfold change in H+ concentration. | H+ (mol/l) | pH | |-------------|----| | 10⁻⁶ | 6 | | 10⁻⁷ | 7 | | 10⁻⁸ | 8 | ## Study Questions 1. What control mechanisms does the body use to maintain the constancy of the internal environment? 2. What consequences would you expect when the body's homeostatic mechanisms break down? 3. How does the percentage of body water vary with age, sex, and body fat? 4. The intracellular compartment is twice as large as the extracellular compartment (ECF) so that its osmolality is only half as that of ECF. Comment. ==End of OCR==