1. The properties of blood

2. Blood is
-a fluid tissue,
-vital vehicle of communication between the tissues and it has very important functions.
It transports:
-O2 from the lungs to the body tissues, CO2 from the tissues to the lungs;
-nutritive substances and metabolites to the tissues and removes waste products;
-distributes hormones from the endocrine glands to the organs they influence.

3. It also helps regulate body temperature by carrying excess heat from the interior of the body to the surface layers of the skin, where the heat is dissipated to the surrounding air.
Other functions are:
immunological role because of intervention of leucocytes;
intervention in stopping hemorrhage by intervention of platelets.

4. Blood consists of a fluid part called plasma in which are suspended formed elements: red cells or erythrocytes, white cells or leukocytes and platelets or trombocytes. Plasma accounts – 55% of the volume and the formed elements account for about 45 %.

5. 1. The blood volume
is especially important in the control of cardiovascular dynamics;
the normal total circulating blood volume of adults is about 8 % of body weight
( about 5 liters in a 70 kg man);
about 1 liter will be in the lungs, about 3 liters in the systemic venous circulation and the remaining liter in the heart, systemic arteries, arterioles and capillaries.

6. 1. The blood volume
The measurement of blood volume can be done by the dilution of specific markers.
For a marker to permit the accurate measurement of the volume of a particular compartment it must be evenly distributed throughout that compartment and it should not be metabolized or alter any physiological variable.

7. 1. The blood volume
To measure plasma volume, a substance must be used that does not penetrate capillary membranes but remains in the vascular system after injection;
serum albumin labeled with radioactive iodine (125I-albumin) or
dyes that avidly bind to the plasma proteins, such as Evans blue dye ;
As the amount of a marker that was injected is known, it is a simple matter to calculate the volume in whichit has been diluted.
Concentration = amount of dye/volume →
volume = amount of dye/concentration

8. If one measures plasma volume using the methods described earlier, blood volume can also be calculated if one knows the hematocrit using the following equation:

9. Physiological and pathological variations
A. Physiological: -Increased in males, in pregnancy by % due to plasma volume, trained personnel, altitude, massive fluid ingestion (transient), heat exposure, -Falls in the elderly, dehydration, the transition from supine to standing, obese people B. Pathological: -Increase in polycythemia -Decreases after hemorrhage and shock.

10. Regulation of blood volume
Plasma volume adjustment is done by reflex and humoral mechanisms. 1. Reflex mechanism: volume receptors in the left atria are sensitive for changes in blood volume; when blood volume increased → atria distension→impulses to nc. solitary tract (brainstem) by vagus nerves → anterior hypothalamus -reflex reduction in ADH secretion → eliminates excess water through urine restoring blood volume.

11. Regulation of blood volume
-cardioaortici sinocarotidieni baroreceptors: increased cardiac output and blood pressure excites baroreceptors triggering a similar reflex (to the one of stimulation of volume receptors).
Blood volume reduction→ decreased blood pressure → reflex vasoconstrictor of renal vessels with glomerular filtration decreased → fluid retention in the body. Reflexes initiated by volume receptors bring the blood volume to normal in about 1 h, but they adapt completely within 1-3 days.

12. Regulation of blood volume
2. Humoral regulation involve:
ADH Aldosterone
Atrial natriuretic factor Plasma proteins

13. Regulation of blood volume
ADH is a hormone secreted by the anterior hipotalamus and stored in posterior pituitary. Secretion is controlled by reflex mechanisms and by the value of osmotic pressure of blood: increase of osmotic pressure  stimulates ADH secretion  retains water in the body.
Aldosterone is a hormone secreted by adrenal glands. It stimulates reabsorption of Na+ and Cl- followed by osmotic water reabsorption in renal tubules leading to reduced urine volume.

14. Regulation of blood volume
Atrial natriuretic factor is a hormone secreted in the walls of the atria (especially right atria). When blood volume increased → atria distension → ANF release → increases Na+ excretion by the kidneys → reduced blood volume.
Plasma proteins retain water in the circulator tree because of their colloid osmotic pressure. When protein levels are below 5.5 g% water passes in the interstitial space causing edema.

15. Regulation of blood volume
Adjustment of the corpuscular volume is made according to the degree of tissue oxygenation:
hypoxia (low concentration of O2 at tissue level) stimulates erythropoiesis leading to increased globular volume.

16. 2. The colour is red in arteries and darker red in veins, the explanation being the oxidation or reduction of hemoglobin.
3. ph 7,35-7,45
4. Normal density of the blood is 1, ,060; the blood density is given by the blood cells, the organic substances, especially the proteins, the mineral substances dissolved in plasma.
As the mineral substances present in plasma are
maintained at strictly constant level, the variations of the plasma density are dependent mainly on:
the number of the blood cells (hematocrit);
the concentration of the proteins (proteinemia);
the concentration of the hemoglobin.

17. Plasma density = 1.024 - 1.028 (average 1.027)
Deproteinated plasma density = 1.006
Physiological variations
1. Increased: perspiration (loss of water); during exercise (the spleen contracts); altitude (increased number of erythrocytes)
2. Decreased: in the period of pregnancy (the plasma volume increases with 20-30%), after massive ingestion of liquids.
Pathological variations
1. Increased values: diarrhea, vomiting, polycythemia (Vera and secondary polycythemia), shock (hem concentration)
2. Decreased values: anemia,hemorrhage (bleeding).

18. 5. Viscosity of plasma depend on these factors: number and size of RBCs, their load in HGB; number and size of WBC; number and size of PLT;
6. Clotting occurs when blood is taken out of the vessels that circulate blood normal. Coagulation represents the transformation from liquid to solid, gelatinous dish in the form in which it is.
After 2-3 hours early clotting table blood is divided into two parts: a solid red and called clot and some liquid, transparent and slightly yellowish serum called serum.

19. 7. Osmotic pressure is the pressure which needs to be applied to a solution to prevent the inward flow of water across a semipermeable membrane. It is also defined as the minimum pressure needed to nullify osmosis.
Hypertonicity is the presence of a solution that causes cells to shrink.
Hypotonicity is the presence of a solution that causes cells to swell.
Isotonic is the presence of a solution that produces no change in cell volume.

20. When the osmotic pressure of the solution outside the blood cells in higher than the osmotic pressure inside the red blood cells, the solution is hypertonic. The water inside the blood cells exits the cells in an attempt to equalize the osmotic pressure (the cells shrink).
When the osmotic pressure outside the red blood cells is the same as the pressure inside the cells, the solution is isotonic with respect to the cytoplasm. This is the usual condition of red blood cells in plasma. The cells are normal.
When the solution outside of the red blood cells has a lower osmotic pressure than the cytoplasm of the red blood cells, the solution is hypotonic with respect to the cells. The cells take in water in an attempt to equalize the osmotic pressure, causing them to swell and potentially burst.

21. 8. Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins in blood plasma that usually tends to pull water into the circulatory system.
Because large plasma proteins cannot easily cross through the capillary walls, their effect on the osmotic pressure of the capillary interiors will, to some extent, balance out the tendency for fluid to leak out of the capillaries.
Or, the oncotic pressure tends to pull fluid into the capillaries. In conditions where plasma proteins are reduced, e.g. from being lost in the urine (proteinuria) or from malnutrition, there will be a reduction in oncotic pressure and an increase in filtration across the capillary, resulting in excess fluid buildup in the tissues (edema).

22. The large majority of oncotic pressure in capillaries is generated by the presence of albumin which constitute approximately 80% of the total oncotic pressure exerted by blood plasma on interstitial fluid.
The total oncotic pressure of an average capillary is about 28 mmHg with albumin contributing approximately 22 mmHg of this oncotic pressure. Because blood proteins cannot escape through capillary endothelium, oncotic pressure of capillary beds tends to draw water into the vessels.

23. Plasma and its balances:
hydro-electrolytic, acid base. Composition of plasma. Physiology of plasma proteins

24. The fluid portion of the blood, the plasma, is a solution containing an important number of ions, inorganic molecules and organic molecules.
The normal plasma volume is about 5% of body weight, or roughly mL in a 70-kg man.

25. The plasma consists of 90% water and the remaining 10% being made up by a variety of substances in solution and suspension.
These include mineral ions (e.g. sodium, potassium, calcium, chloride), small organic molecules (glucose, aminoacids, fatty acids) and plasma proteins.
The major constituents of the plasma, proteins and inorganic ions are normally present at roughly constant levels.

27. The chief inorganic cation of plasma is sodium and chloride is the principal anion of the plasma.
The ionic components of the plasma maintain both its osmolality ( mOsm per kg water) and its pH(7,35- 7,45) within physiological limits.

28. Plasma Proteins
The plasma proteins consist of albumin, globulin, and fibrinogen fractions and the globulin fraction is subdivided into numerous components.
One classification divides it into α1,α2, β and γ globulins and fibrinogen.
Most of the plasma proteins are synthesized in the liver; other are produced in the plasma cells(leukocytes).

30. The total amount of protein in plasma- proteinemia; normal values ​​are 6.5 -8 g%.
Proteinemia that is more than 8 g% is called hyperproteineamia and when it is less than 6 g% is called hypoproteinaemia.
Plasma protein levels are maintained during starvation until body protein stores are markedly depleted. In prolonged starvation, malabsorbtion syndrome due to intestinal diseases, liver disease, nephrosis plasma protein levels are low. The consequence is decrease in the plasma oncotic pressure and edema tends to develop.

31. Acid-Base Balance

32. Precise H+ regulation is essential because the activities of almost all enzyme systems in the body are influenced by H+ concentration.
Therefore, changes in hydrogen concentration alter virtually all cell and body functions.
Compared with other ions, the H+ concentration of the body fluids normally is kept at a low level.
To achieve homeostasis, there must be a balance between the intake or production of H+ and the net removal of H+ from the body

33. HCO3 – + H+ → H2CO3 → HCO3 – + H+
A strong acid is one that rapidly dissociates and releases especially large amounts of H+ in solution (HCl). Weak acids have less tendency to dissociate their ions and, therefore, release H+ with less vigor. An example is H2CO3.
A strong base is one that reacts rapidly and strongly with H+ and, therefore, quickly removes these from a solution.

34. The blood H+ concentration is normally maintained within tight limits around a normal value of about 40 nEq/L. Normal variations are only about 3 to 5 nEq/L
pH = -log[ H+]

35. Because the normal pH of arterial blood is 7
Because the normal pH of arterial blood is 7.4, a person is considered to have acidosis when the pH falls below this value and to have alkalosis when the pH rises above 7.45. pH
Extracellular fluid
Arterial blood
7.45
Venous blood
7.35
Interstitial fluid
Intracellular fluid
6-7.4
Urine
4.5-8
Gastric HCl
0.8

36. There are two primary systems that regulate the H+ concentration :
(1) the chemical acid-base buffer systems of the body fluids- immediately combine with acid or base to prevent excessive changes in [H+];
(2) the biological systems:
respiratory center, regulates the removal of CO2 (and, therefore, H2CO3) from the extracellular fluid; acts within a few minutes to eliminate CO2 and, therefore, H2CO3 from the body;
the kidneys, which can excrete either acid or alkaline urine, thereby readjusting the extracellular fluid H+ concentration

37. A buffer is any substance that can reversibly bind H+
Buffer + H ↔ H Buffer
A free H+ combines with the buffer to form a weak acid (H buffer) that can either remain as an unassociated molecule or dissociate back to buffer and H+. When the H+ concentration increases, the reaction is forced to the right, and more H+ binds to the buffer, as long as buffer is available. Conversely, when the H+ concentration decreases, the reaction shifts toward the left, and H+ is released from the buffer.
In this way, changes in H+ concentration are minimized.

38. The bicarbonate buffer system consists of a water solution that contains two ingredients: a weak acid, H2CO3, and a bicarbonate salt, such as NaHCO3.
H2CO3 is formed in the body by the reaction of CO2 with H2O.
CO2 + H2O  H2CO3  CO2 + H2O

39. The second component of the system, bicarbonate salt, occurs predominantly as sodium bicarbonate (NaHCO3) in the extracellular fluid.
NaHCO3 ionizes almost completely to form HCO3 – and Na+
NaHCO3 → Na+ + HCO3-

40. H+ + HCO3- → H2CO3  CO2 + H2O
Na OH + H2CO3 →NaHCO3 + H2O

41. All acids, including H2CO3, are ionized to some extent.
For any acid, the concentration of the acid relative to its dissociated ions is defined by the dissociation constant K.
H+ x HCO3-
K =
H2CO3

42. The concentration of undissociated H2CO3 cannot be measured in solution because it rapidly dissociates into CO2 and H2O or to H+ and HCO3 –.
the CO2 dissolved in the blood is directly proportional to the amount of undissociated H2CO3.
H2CO3=0.03 x p CO2

43. The dissolved carbon dioxide in the blood reacts with water to form carbonic acid. This reaction would occur much too slowly .
inside the RBCs -carbonic anhydrase, which catalyzes the reaction between carbon dioxide and water and accelerates its reaction rate about fold.
The reaction occurs so rapidly in the red blood cells that it reaches almost complete equilibrium within a very small fraction of a second and this allows tremendous amounts of carbon dioxide to react with the red blood cell water even before the blood leaves the tissue capillaries.

45. The Henderson-Hasselbalch equation, in addition to defining the determinants of normal pH regulation and acid-base balance in the extracellular fluid, provides insight into the physiologic control of acid and base composition of the extracellular fluid.
pH= pK +log [HCO3-]/[H2CO3]

46. From the Henderson-Hasselbalch equation, it is apparent that
an increase in HCO3– concentration causes the pH to rise, shifting the acid-base balance toward alkalosis.
an increase in pCO2 causes the pH to decrease, shifting the acid-base balance toward acidosis.

47. When disturbances of acid-base balance result from a primary change in extracellular fluid bicarbonate concentration, they are referred to as metabolic acid-base disorders
metabolic acidosis, caused by a primary decrease in bicarbonate concentration
metabolic alkalosis primary increase in bicarbonate concentration
Acidosis caused by an increase in pCO2 is called respiratory acidosis, whereas alkalosis caused by a decrease in PCO2 is termed respiratory alkalosis.

48. The bicarbonate buffer system is the most powerful extracellular buffer in the body.
This apparent paradox is due mainly to the fact that the two elements of the buffer system, HCO3 – and CO2, are regulated, respectively, by the kidneys and the lungs.

49. Phosphate buffer system are H2PO4 – and
Proteins are among the most plentiful buffers in the body because of their high concentrations, especially within the cells.
60 to 70 % of the total chemical buffering of the body fluids is inside the cells, and most of this results from the intracellular proteins.
In the red blood cell, hemoglobin (Hb) is an important buffer, as follows:
H+ + Hb ↔HHb

50. The second line of defense against acid-base disturbances is control of extracellular fluid CO2 concentration by the lungs.
An increase in ventilation eliminates CO2 from extracellular fluid, which, by mass action, reduces the H+ concentration. Conversely, decreased ventilation increases CO2, thus also increasing H+ concentration in the extracellular fluid.
CO2 is formed continually; it diffuses into the interstitial fluids and blood, and the flowing blood transports it to the lungs, where it diffuses into the alveoli and then is transferred to the atmosphere by pulmonary ventilation.

51. The alveolar ventilation rate increases four to five times normal as the pH decreases from the normal value of 7.4 to the strongly acidic value of 7.0. Conversely, when plasma pH rises above 7.4, this causes a decrease in the ventilation rate.
Because increased H+ concentration stimulates respiration, and because increased alveolar ventilation decreases the H+ concentration, the respiratory system acts as a typical negative feedback controller of H+ concentration.

52. The kidneys control acid-base balance by excreting either an acidic or a basic urine. Excreting an acidic urine reduces the amount of acid in extracellular fluid, whereas excreting a basic urine removes base from the extracellular fluid.

53. Large numbers of HCO3 – are filtered continuously into the tubules, and if they are excreted into the urine, this removes base from the blood.
Large numbers of H+ are also secreted into the tubular lumen by the tubular epithelial cells, thus removing acid from the blood. If more H+ is secreted than HCO3 – is filtered, there will be a net loss of acid from the extracellular fluid.
Conversely, if more HCO3 – is filtered than H+ is secreted,there will be a net loss of base.

54. Each day the body produces about 80 milliequivalents of nonvolatile acids, mainly from the metabolism of proteins.
These acids are called nonvolatile because they are not H2CO3 and, therefore, cannot be excreted by the lungs. The primary mechanism for removal of these acids from the body is renal excretion.

55. When there is a reduction in the extracellular fluid H+ concentration (alkalosis), the kidneys fail to reabsorb all the filtered bicarbonate, thereby increasing the excretion of bicarbonate.
Because HCO3 – normally buffers hydrogen in the extracellular fluid, this loss of bicarbonate is the same as adding an H+ to the extracellular fluid.
Therefore, in alkalosis, the removal of HCO3 – raises the extracellular fluid H+ concentration back toward normal.

56. In acidosis, the kidneys do not excrete bicarbonate into the urine but reabsorb all the filtered bicarbonate and produce new bicarbonate, which is added back to the extracellular fluid.
This reduces the extracellular fluid H+ concentration back toward normal

57. Thus, the kidneys regulate extracellular fluid H+ concentration through three fundamental mechanisms:
secretion of H+,
reabsorption of filtered HCO3-, and
production of new HCO3 .

58. Referring to Henderson- Hasselbalch equation, we can see that acidosis occurs when the ratio of HCO3– to CO2 in the extracellular fluid decreases, thereby decreasing pH.
If this ratio decreases because of a fall in HCO3 –, the acidosis is referred to as metabolic acidosis. If the pH falls because of an increase in PCO2, the acidosis is referred to as respiratory acidosis.

59. pH
Pco2
HCO3-
HCO3- / H2CO3
Normal
7.4
40 mmHg
24 mEq/l
18-22
Respiratory acidosis ↓ ↑↑ ↑
< 18
Respiratory alkalosis ↓↓
> 22
Metabolic acidosis
Metabolic alkalosis

60. In metabolic acidosis, the primary abnormality is a decrease in plasma HCO3–.
The primary compensations include increased ventilation rate, which reduces pCO2, and renal compensation, which, by adding new bicarbonate to the extracellular fluid, helps minimize the initial fall in extracellular HCO3 - concentration.

61. The compensatory responses to alkalosis are basically opposite to those that occur in acidosis.
In alkalosis, the ratio of HCO3 – to CO2 in the extracellular fluid increases, causing a rise in pH (a decrease in H+ concentration), as is evident from the Henderson- Hasselbalch equation.

62. In respiratory acidosis, the compensatory responses available are (1) the buffers of the body fluids and (2) the kidneys, which require several days to compensate for the disorder.
Respiratory alkalosis is caused by overventilation by the lungs. Rarely does this occur because of physical pathological conditions.