1.1 Cell Physiology of the human cell.pptx

what is human physiology and the principally at the level of organisms and systems

1. CELL PHYSIOLOGY UNIT 1 Dr Lwiindi L Medical School UNZA (BVM, BSc.HB , MBChB ( prog ), MSc. HP)

2. What is Physiology? Human physiology is the described as the science of the mechanical, physical, and biochemical functions of humans in good health, their organs, and the cells of which they are composed. It focuses principally at the level of organs and systems.

3. Total Body Water 1. Intracellular fluid (ICF): 2. Extracellular fluid (ECF): -Interstitial fluid (ISF): -Vascular fluid (VF): Body Compartment DISTRIBUTION OF FLUIDS WITHIN THE BODY ?

4. DISTRIBUTION OF FLUIDS WITHIN THE BODY Total Body Water Intracellular fluid (ICF): approximately 2/3 of total of body water Extracellular fluid (ECF): approximately 1/3 of total body water Interstitial fluid (ISF): approximately 2/3 of the extracellular fluid Vascular fluid (VF): approximately 1/3 of the extracellular fluid (plasma plus red blood cells).A normal vascular volume is close to 5 L (blood volume).

5. Figure 1.1 :Fluid compartments of the body. Volumes are for an average 70-kg (154-lb) person. TBW total body water; ECF extracellular fluid.

6. Compartmentalization is an important general principle in physiology. In animals with a closed vascular system, the ECF is divided into two components: the interstitial fluid and the circulating blood plasma. The plasma and the cellular elements of the blood, principally red blood cells, fill the vascular system, and together they constitute the total blood volume. The interstitial fluid is that part of the ECF that is outside the vascular system, bathing the cells. On average, 60% (42L) of the body weight of young adult male is water The remaining18% of the body weight is protein and related substances, 7% is mineral, and 15% is fat.

7. Approximately 80 percent of the extracellular fluid surrounds all the body’s cells except the blood cells. Because it lies “between cells,” this 80 percent of the extracellular fluid is known as interstitial fluid. The remaining 20 percent of the extracellular fluid is the fluid portion of the blood, the plasma, in which the various blood cells are suspended. Intracellular fluid ( lCF ) versus Extracellular fluid(ECF) These two compartments are separated by cell membranes which generally have the following important characteristics: Freely Permeable to Water: In a steady state, intracellular and extracellular osmolarity will be the same. Normally, this is 295 mOsmo (close to 300 mOsm ). Impermeable to Sodium (Chloride): The difference in the concentration of impermeable particles determines the osmotic movement of water across membranes. The concentration of these particles is often referred to as the effective osmolarity of a particular compartment.

8. Blood Volume Blood contains both extracellular fluid (the fluid in plasma) and intracellular fluid (the fluid in the red blood cells). However, blood is considered to be a separate fluid compartment because it is contained in a chamber of its own, the circulatory system. The blood volume is especially important in the control of cardiovascular dynamics. The average blood volume of adults is about 7 per cent of body weight, or about 5 liters. About 60 per cent of the blood is plasma and 40 per cent is red blood cells, but these percentages can vary considerably in different people, depending on gender, weight, and other factors.

9. Hematocrit (Packed Red Cell Volume). The hematocrit is the fraction of the blood composed of red blood cells, as determined by centrifuging blood in a “ hematocrit tube” until the cells become tightly packed in the bottom of the tube. It is impossible to completely pack the red cells together; therefore, about 3 to 4 per cent of the plasma remains entrapped among the cells, and the true hematocrit is only about 96 per cent of the measured hematocrit . In men, the measured hematocrit is normally about 0.40, and in women, it is about 0.36. In severe anemia, the hematocrit may fall as low as 0.10, a value that is barely sufficient to sustain life. Conversely, there are some conditions in which there is excessive production of red blood cells, resulting in polycythemia . In these conditions, the hematocrit can rise to 0.65.

10. FACTORS AFFECTING Total Body H 2 O varies depending on body fat: Infant: 73-80% Male adult: 60% Female adult: 40-50% Effects of obesity Old age 45% Climate Level of physical activity

11. PERCENTAGE OF H2O IN TISSUES

12. Summary Total body water (as percentage of body weight) in relation to age and sex.

13. Constituents of Extracellular and Intracellular Fluids Comparisons of the composition of the extracellular fluid, including the plasma and interstitial fluid, and the intracellular fluid are shown in Figures 1–2 and 25–3 and in Table 25–2.

14. APPROXIMATE IONIC COMPOSITION OF THE BODY H2O COMPARTMENTS

15. Important Constituents of the Intracellular Fluid The intracellular fluid is separated from the extracellular fluid by a cell membrane that is highly permeable to water but not to most of the electrolytes in the body. In contrast to the extracellular fluid, the intracellular fluid contains only small quantities of sodium and chloride ions and almost no calcium ions. Instead, it contains large amounts of potassium and phosphate ions plus moderate quantities of magnesium and sulfate ions, all of which have low concentrations in the extracellular fluid. Also, cells contain large amounts of protein, almost four times as much as in the plasma.

16. CRITERIA FOR A SUITABEL DYE FOR MEASURING COMPARTMENT. (BODY FLUID MARKER) Must mix evenly throughout the compartment Non toxic, no physiological activity Even mixing Must have no effect of its own on the distribution of H2O or other substances in the body Either it must be unchanged during the experiment or if it changes , the amount changed must be known. The material should be relatively easy to measure .

17. DILUTION PRINCIPLE Inject x gm of marker into compartment measure concentration at equilibrium (y gm/L) Since concentration = mass/ volume concentration = mass / Volume = x/y L C1V1=C2V2 Principle of mass conservation Based on using a marker whose concentration can be measured .

18. Measuring Compartment Size Indirect METHOD – INDICATOR (DYE) DILUTION TECHN IQUE (Law of Mass Conservation) Concentration = Amount Injected Volume of Distribution Compartment Volume (V) Tracer Concentration (C) Amount of Tracer Added (A) Amount of Tracer Lost From Compartment (E) Based on concentration in a well-mixed substance that distributes itself only in the compartment of interest.

19. Measuring Compartment Size ….. Amount of Tracer Remained in Compartment = A - E Compartment Volume = (A – E)/C Therefore the volume of distribution is equal to the amount injected (minus any that has been removed from the body by metabolism or excretion during the time allowed for mixing) divided by the concentration of the substance in the sample.

20. Example: 150 mg of sucrose is injected into a 70 kg man. The plasma sucrose level after mixing is 0.01 mg/ mL , and 10 mg has been excreted or metabolized during the mixing period. The volume of distribution of the sucrose is Since 14,000 mL is the space in which the sucrose was distributed, it is also called the sucrose space. Example

21. Take this problem: 100 mg of sucrose is injected into a 70 kg man. The plasma sucrose level after mixing is 0.01 mg/ml. If 5 mg has been metabolized during this period, then, what is the ECF volume? 9.5 L 14 L 17.5 L 10 L ??????? If 1mL of solution (10mg/ mL ) of dye is dispersed in chamber B and final concentration is the chamber is 0.01mg/ mL. What is the volume in chamber B? 1000ml or 1L

22. Indicators used for measuring plasma volume, ECF volume and total body H 2 O Compartment Criterion Indicators Plasma Substance should not cross capillaries Evans blue dye; radioiodinated fibrinogen; radioiodinated albumin ECF volume Substance should cross capillaries but not cross cell membranes Isotonic solutions of sucrose, inulin , mannitol , NaCl Total body H 2 O (TBW) Substance distributes evenly in ICF & ECF Heavy H2O, tritiated H2O, aminopyrine , antipyrine

23. Total Body H 2 O (TBW) Deuterated H2O (D 2 O) Tritiated H2O (TH 2 O) Antipyrine

24. Radioactive water (tritium, 3 H 2 O) or heavy water (deuterium, 2 H 2 O) can be used to measure total body water. These forms of water mix with the total body water within a few hours after being injected into the blood, and the dilution principle can be used to calculate total body water Another substance that has been used to measure total body water is antipyrine , which is very lipid soluble and can rapidly penetrate cell membranes and distribute itself uniformly throughout the intracellular and extracellular compartments. Total Body H 2 O (TBW) Cont…….

25. Blood volume /Markers used Obtained from plasma volume and hematocrit Total blood volume = Plasma volume/1- Hematocrit Example: If the plasma volume is 4 liters and the hematocrit is 0.45, total blood volume is ? =PLASME VOL X 100 100 –HCT 1.T-1824 (Evans blue dye) attaches to plasma proteins and is removed by the liver. Measures plasma volume 2. Radioactive labeled 125 i albumin 3. Cr 51 (radioactive chromium) is incubated with red blood cells then injected Measures total blood volume

26. Compartments with no Compartment-Specific Substance Determine by subtraction: How would you measure ICF volume? Cannot be measured; it is calculated (estimated).. ICF volume = Total body H 2 O – ECF volume Interstitial volume Can not be measured directly Interstitial Fluid Volume (ISFV). ISFV = ECFV - PV

27. If one knows the plasma volume and the hematocrit the total blood volume can be calculated by multiplying the plasma volume by Example: The hematocrit is 38 and the plasma volume 3500 mL. The total blood volume is The red cell volume (volume occupied by all the circulating red cells in the body) can be determined by subtracting the plasma volume from the total blood volume. It may also be measured independently by injecting tagged red blood cells and, after mixing has occurred, measuring the fraction of the red cells that is tagged.

28. Measurement of other spaces Extracellular volume Na 24 Cl 35 Inulin Sucrose Mannitol Sulfat e I 125 iothalamate Disperse in plasma and interstitial fluid, but not permeable to cell membrane 30-60 min for dispersion to extracellular fluid

29. Determining body fat: Technique: bioelectric impedance technique Principle: Body fluids conduct electricity well; But fat is anhydrous and therefore is a poor conductor of electricity; The resistance to flow of a small current between points on the body is proportional to fat mass.

30. Lean body mass (LBM ) Definition: LBM is fat free mass Total body mass = fat mass + fat free mass Note: fat is relatively anhydrous Note: the H 2 O content of LBM is constant H 2 O content of LBM is constant - 70 ml /100 g tissue

31. Take this problem : In a healthy adult male weighing 70 kg, total body H 2 O (TBW) was measured to be 42 L. What is his lean body mass (LBM)? What is his fat mass? Given TBW = 42 L Assume all this H 2 O is in LBM & that fat is H 2 O free We know that H 2 O content of LBM is 70 ml/100 g Thus, if TBW is 42 L, LBM = 60 kg Since he weights 70 kg, his fat mass is 70-60 = 10 kg

32. Osmolarity and osmolality The osmolarity is the number of osmoles per liter of solution- eg , plasma-whereas the osmolality is the number of osmoles per kilogram of solvent. Therefore, osmolarity is affected by the volume of the various solutes in the solution and the temperature, while the osmolality is not. Osmotically active substances in the body are dissolved in water, and the density of water is 1, so osmolal concentrations can be expressed as osmoles per liter ( osm /L) of water. , osmolal (rather than osmolar ) concentrations are considered, and osmolality is expressed in milliosmoles per liter (of water).

33. Osmolal Concentration of Plasma: Tonicity The freezing point of normal human plasma averages -0.54 °C, which corresponds to an osmolal concentration in plasma of 290 mosm /L. This is equivalent to an osmotic pressure against pure water of 7.3 atmospheres. The osmolality might be expected to be higher than this, because the sum of all the cation and anion equivalents in plasma is over 300. It is not this high because plasma is not an ideal solution and ionic interactions reduce the number of particles free to exert an osmotic effect. Except when there has been insufficient time after a sudden change in composition for equilibrium to occur, all fluid compartments of the body are in or nearly in osmotic equilibrium.

34. The term tonicity is used to describe the osmolality of a solution relative to plasma. Solutions that have the same osmolality as plasma are said to be isotonic; those with greater osmolality are hypertonic; and those with lesser osmolality are hypotonic. All solutions that are initially isosmotic with plasma- i.e , that have the same actual osmotic pressure or freezing-point depression as plasma-would remain isotonic if it were not for the fact that some solutes diffuse into cells and others are metabolized. Thus, a 0.9% saline solution remains isotonic because there is no net movement of the osmotically active particles in the solution into cells and the particles are not metabolized. On the other hand, a 5% glucose solution is isotonic when initially infused intravenously, but glucose is metabolized, so the net effect is that of infusing a hypotonic solution.

35. It is important to note the relative contributions of the various plasma components to the total osmolal concentration of plasma. All but about 20 of the 290 mOsm in each liter of normal plasma are contributed by Na + and its accompanying anions, principally Cl - and HCO 3- Other cations and anions make a relatively small contribution. Although the concentration of the plasma proteins is large when expressed in grams per liter, they normally contribute less than 2 m Osm /L because of their very high molecular weights.

36. The major nonelectrolytes of plasma are glucose and urea, which in the steady state are in equilibrium with cells. Their contributions to osmolality are normally about 5 mOsm /L each but can become quite large in hyperglycemia or uremia. The total plasma osmolality is important in assessing dehydration, overhydration , and other fluid and electrolyte abnormalities. Hyperosmolality can cause coma ( hyperosmolar coma).