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Blood Physiology
Main blood functions
• Medium of transport - Gases(O2 and Co2)
- Nutrients (CHO, aa, lipids & vitamins)
- Ions (Na+, Ca2+ , HCO3−)
- Metabolic wastes (urea)
- Hormones and enzymes
• Maintains homeostasis - Body temperature regulation
- PH regulation(acid-base balance)
- Osmolarity and regulation of water balance
• Defense - Prevents infections (WBC’s, Neutrophiles & Monocytes)
2
Introduction
Properties of blood
a. Viscosity - refers to internal resistance of a liquid to flow.
- blood is 3X thicker and denser than pure water.
b. Ph - normal interval is 7.35-7.45.
- blood is slightly alkaline.
c. Volume - 8% of total body weight.
- male(5-6 Lit) and female(4-5 lit)
d. Temperature - slightly warmer than body temperature
e. Color - bright red (oxygenated blood)
- dark red (venous blood, deoxygenated)
Components of Blood
• Blood is a connective tissue that consists of:
1. Plasma (55% or 3 Lit.):
o Nonliving extracellular matrix
o Fluid portion
2. Formed elements (45% or 2 Lit)
o Living cells
o Three types - RBC (Erythrocytes),
- WBC (Leukocytes) and
- Platelets (Thrombocytes)
5
The Haematocrit (Hct) or PCV
• Un-coagulated blood is centrifuged at high speed (3000 rpm) for
(5 to10 min), 3-layers form after centrifugation
1. Upper suspension - is the blood plasma accounts to about 55% of
the blood volume.
2. Middle buffy coat - accounts to < 1% of the blood volume.
- consists of WBC and Platelets
3. Lower portion - is a reddish mass of RBC that settles at the
bottom of the test tube.
- accounts to about 45% of the total bloo vol.
6
The Haematocrit (Hct) or PCV
7
The Haematocrit (Hct) or PCV
• Blood plasma contains:
o More than 33 different substances .
o Organic molecules, water, elctrolytes, gases etc.
o
8
Blood Plasma components
Serum vs. plasma
• Serum is the yellowish fluid that forms after blood is left to
clot.
• Serum has more or less similar composition to plasma
except that its fibrinogen have been removed.
So, serum is blood without fibrinogen.
9
Blood Plasma components
10
Plasma proteins
A. Albumin (~ 60% or 4.5 gm/dl)
B. Globulins ( ~ 40%, or 2.5 g/dl)
C. Fibrinogen (0.3 g/dl)
• Determined by means of
electrophoresis
Blood Plasma components
11
Blood Plasma components
13
Types of blood cells:
• RBCs (Erythrocytes)
= 5,000,000 /mm3
• WBCs (Leucocytes)
= 5,000 / mm3
• Platelets (Thrombocytes)
= 200,000 / mm3
Blood Cells (Formed elements)
14
RBC (Erythrocytes)
Properties
• Biconcave shape
• Non-nucleated
• Diamter = 7.5 um.
• Very flexible
• Number =4.7-5 x106
• Develop in about 15 days
• Life span is about 120 days
• Produce in red bone marrow
Hemoglobin (Hg) – red pigment of RBCs.
• Functions - transports O2 & CO2
- Serves as a buffer to maintain acid-base balance.
• Structure - Hg has two parts
a. Globin part - 4-polypeptide chains (2alpha & 2beta globulins)
b. Heme part - Porphyrin & Fe2+ at the center to w/h O2 binds.
• Each polypeptide has one Heme group and each Heme contains one Fe2+
that carries 1-O2 molecule.
o So, totally, 4O2 molecules are carried by 1-Hb molecule.
15
RBC (Erythrocytes)
• Normal haemoglobin(Hg) values in the blood varies based on
age.
o Infants: 14 – 20 g/dl
o Adult males: 13–18 g/dl
o Adult females: 12–16 g/dl
16
RBC (Erythrocytes)
RBC fragility test (hemolysis)
• Fragility tests are conducted in solutions which have different
tonicities.
• It is conducted to determine the degree of hemolysis of RBC’s.
1.In isotonic solution - 0.9% NaCl solution is isotonic to plasma.
- the size and shape of RBC remains normal
2. Hypertonic solution - greater than 0.9% NaCl solution, RBC-lose
water and shrink
3. Hypotonic solution - lower than normal (<0.9%) NaCl solution, RBC
hemolyse(burst) & lose their Hb to the plasma
17
18
Genesis of RBC’s
• RBC and other blood cells are produced in the bone marrow from a
single type of cells called pluripotent hematopoietic stem cells.
 These cells, then differentiate and form committed stem cells that
produce only specific types of blood cells.
• The committed stem cells that produce :
o Erythroctes - colony-forming unit–erythrocytes (CFU-E).
o Granulocytes - colony forming unit granulocytes
o Monocytes - colony forming unit monocytes
o Platelets - colony forming unit Megakaryocytes
• Lymphoid stem cells - T- and B- Lymphocytes.
Genesis of RBC’s
RBC and ATP production
• How do RBC’s survive if they lose
their nucleus and mitochondria,
o which are responsible for protein
synthesis and oxidative
metabolism, respectively?
Answer:
• Mature RBC’s : Do not synthesize
proteins, but utilize glucose to get
energy by glycolysis
• Moreover, RBC membnrane has a
lot of the enzyme 2-3-DPG, which
promotes release of O2 from Hb as
in high altitudes
22
Erythrocyte Sedimentation Rate (ESR)
• ESR is the rate or speed at which un-coagulated blood (RBC)
settles down when allowed to stand for about 1hour in a tube.
• It is a non-specific test
Factors that affect ESR
a. Polycythemia - Hct value is large, so ESR is low
b. Anemia - ESR is fast, so ESR value is high
23
Regulation of Erythropoesis
• Erythropoesis is the process of RBCs production
which is egulated by -ve feed back mechanism.
o Hypoxia stimulates the kidney & liver to release
erythropoietin hormone
↓
o Erythropoietin reaches bone marrow throgh
blood & induce stem cells to produce more RBC’s
↓
o The RBC’s release O2 to the body
• So, Kidney insufficiency can cause anemia, b/s
of lower synthesis of erythropoietin.
24
25
• Knowing the RBC-indices will help one to realize the size, Hg-level
in the blood, and type of RBC abnormalities or pathologies.
• Thus the 3-important facts that need to be assessed in RBC-indices
includes measuring the:
a. Hg-concentration
b. RBC-count (No of RBCs)
c. Ht (hematocrit) values
RBC-indices
RBC-indices
• From the above indices, other important blood parameters can be
calculated, including:
1. MCV : Mean Cell Volume
2. MCH : Mean Cell Hemoglobin
3. MCHC: Mean Cell Hemoglobin Concentration
26
RBC indices
MCV(mean cell volume):
• Tells size of the RBCs
a. Macrocytic
• RBC that are larger or bigger in size
oe.g. pernicious or megaloblastic
anemia, due to Vit. 12 deficiency)
b. Normocytic
• RBC with normal size ~ 7 UM
c. Microcytic
• RBC that are smaller in size
MCHC (mean cell Hg conc.)
• Tells Fe status
a. Normochromic
• Normal Hb synthjes is 33% g/dl
b. Hypochromic
• Less MCHC( < 33 g/100 ml) values
indicate deficient hemoglobin synt.
c. Hyperchromic
• High MCHC values do not occur,
ob/s the Hb conc. is close to
saturation point in red cells.
27
28
• Anemia means having decreased RBC number or lower
concentration of hemoglobin (Hb) in the circulating blood.
• In anemia, there is a diminished O2-carrying capacity of the blood.
• Generally anemia results from excessive loss (bleeding), or
destruction (hemolysis), or lower production of RBC (lack of
nutrition) in the circulation.
• Types of Anemia: a. Blood loss anemia
b. Aplastic anemia
c. Megaloblastic anemia &
d. Hemolytic anemia
Clinical correlates
a. Blood loss anemia:
• During hemorrhage persons loose too much blood.
• The Fe2+ absorbed from the intestine is not enough to produce
adequate Hgb to replace the lost Hgb that took place during bleeding.
• As the result, the RBC’s produced are smaller in size and have lower
Hb level causing a microcytic, hypocromic anemia.
b. A plastic anemia:
• Aplasia means lack of functioning bone marrow.
• It is caused by exposure to excess chemicals, drugs and gamma or X-
ray that destroy the bone marrow.
29
Clinical correlates
c. Megaloblastic (pernicious) anemia
• Caused by:
o Nutritional deficiency: maturation failure caused by inability to
absorb Vitamin-B12 and folic acid from the intestine.
o Absence of intrinsic factor (gastrechtomy) is another cause.
• Effect is that RBC can not proliferate properly, b/s DNA synthesis
does not occur.
• As the result the RBC’s become big, oversized (megaloblastic ) and
have fragile membranes that easily rupture and decrease the No.
30
Clinical correlates
d. Hemolytic anemia: hereditarily acquired and makes the RBC’s to
easily rupture as they cross thru narrow blood vessels like capillaries.
• Examples are:
1. Hereditary spherocytosis: spherical shaped RBC (not biconcave) that
rupture easily
2. Sickle cell anemia: is caused by abnormal beta chain in Hb-structure.
When exposed to low O2 (hypoxia), the Hb precipitates forming long
crystals and damaging and rupturing the cell-membrane.
3. Erythroblastosis fetalis: Destruction and decrease of RBC’s number
of the fetus by antibodies from Rh-negative mother.
31
Clinical correlates
32
• Polycethemia - high production of RBC in the circulation(7-8 m/ mm3)
• It has a physiological or pathological causes.
A. Physiological cause is known as secondary polycethemia :
• When the tissues become hypoxic b/s of low O2-tension as in high
altitude, the bone marrow produces excessive RBC (6-7 mill/mm3).
B. Pathological cause is called polycethemia vera (erythremia) or primary
polycythemia.
• Caused mainly by genetic factors as in tumerous (cancerous) RBC
production.
• Moreover, increases are also seen in WBC and platelet numbers.
Clinical correlates
The pH Scale:
• The pH scale is a convenient way of designating the concentrations of
H+ and OH- in solution in the range between 1.0 M H+ and 1.0 M OH-.
• PH is the (-) logarithm of [H+] where as POH is the (-) log of [OH]
PH = -log [H ]; POH = -log [OH-].
o Solutions in w/c [H+] = [OH-] are neutral and have PH values = 7.0
o Solutions in which [H+] > [OH-] are acidic and have pH values ˂ 7.0.
o Solutions in which [H+] < [OH-] are basic and have pH values ˃ 7.0.
PH and Regulation of acid-base balance
• PH of the body fluids (acid-base balance ) is regulated by 3
important ways.
A. The buffer system (chemical buffers)
B. The respiratory system (CO2)
C. The renal system ( HCO3)
34
PH and Regulations of acid-base balance
• Buffers are aqueous systems that tend to resist changes in pH
o when small amounts of strong acid [H+] or base [OH-] are added.
• A buffer system consists of a weak acid (the proton donor) and
its conjugate base (the proton acceptor).
• Because buffer systems have both HA and A- species, they are
capable of absorbing either strong base or strong acid
• E.g. a mixture of equal concentrations of acetic acid and acetate
ion is a buffer system.
A. The Buffer System
• Strong acids (HCl and H2SO4 ) strong bases (NaOH and KOH )are are
complately ionized in aqueous solutions.
HCl  H+ + Cl- (strong acid)
NaOH  Na+ + OH- (strong base)
• Weak acids(acetic acid, lactic acid, carbonic acids) and weak bases
(MgOH, AlOH)are not completely ionized when dissolved in water.
o Instead, depending upon the pH, both the proton donor species
(conjugate acid) and proton acceptor species (the conjugate base)
occur together in solution.
A. The Buffer System
• Each weak acid has a characteristic tendency to lose its proton in
aqueous solution.
HA H+ + A-
• PH of the buffers is calculated by the Henderson-Hasselbach
equation.
• PH = pKa+ log Conjugate base = pKa + log [A-] / [HA]
Weak acid
Ka – equilibrium constant
A. The Buffer System
• There are 4-types of chemical buffers, w/c are intracellular
(ICF) and extracellular (ECF)
• These are:
1. Bicarbonate/carbonic acid buffer system(ECF)
2. Protein buffer system (ICF or ECF)
3. Hemoglobin buffer system (ICF)
4. Phosphate buffer system (ICF)
38
A. The Buffer System
1. Bicarbonate/carbonic acid buffer system
• The most important buffer of the plasma is the bicarbonate/
carbonic acid buffer system
• The ratio of base to acid (HCO3-/H2CO3) is nearly 20/1 in plasma
under physiological conditions
o i.e. HCO3
-/H2CO3 = 20/1, when plasma pH=7.4
• This buffer system is more complex than others,
o Because carbonic acid (H2CO3) is formed from dissolved CO2
which produced in tissues and diffused to plasma.
CO2 + H2O H2CO3 HCO3
- + H+
• This reaction is slow in plasma but in erythrocytes, carbonic
anhydrase increases the rate of this reaction.
• When hydrogen ion concentration increases in plasma, HCO3
- ions
bind to H+ forming H2CO3.
o H2CO3 is dissociated to CO2 + H2O
o The extra CO2 is then released to the atmosphere by lungs
1. Bicarbonate/carbonic acid buffer system
2. Protein buffer system
• If pH climbs, the carboxyl group of amino acid acts as a weak acid
• If the pH drops, the amino group acts as a weak base
• Proteins are much more effective buffers in intracellular medium.
• Buffering effect of proteins is low in plasma
o Proteins, especially albumin, accounts for 95% of the non-
bicarbonate buffer value of the plasma.
2. Protein buffer system
3. Hemoglobin buffer system
• Prevents pH changes when PCO2 is rising or falling
• Hemoglobin (Hg) is a protein which carries O2 to tissues and CO2
from tissues to lungs and is an effective buffer.
• Around 95% of CO2 released from tissues to plasma is diffused
into erythrocytes.
• In erythrocytes, carbonic anhydrase catalyzes the formation of
H2CO3 from CO2 and H2O which in turn dissociates to HCO3
- & H+.
Carbonic anhydrase
• CO2 + H2O H2CO3 HCO3
- + H+
• Released protons take part in the formation of salt bridges
between globin chains of Hb, and lead the change in the
conformation of Hb molecule in tissue capillaries.
2. Hemoglobin buffer system
4. The Phosphate buffer system
• Phosphate buffer system is most effective in intracellular
medium, especially in kidneys.
• Phosphate buffer system is not effective in plasma, because
phosphate ion concentrations are low.
• However it is important in the excretion of acids in the urine.
o H+ secrected into the tubular lumen by the Na+–K+ exchanger
react with HPO4
2- to form H2PO4
-.
• Some organic phosphates (2,3 diphosphoglycerate in
erythrocytes) has also buffering capacity.
• The pH of the ECF remains between 7.35 and 7.45
o If plasma level: - fall below 7.35 → acidosis
- rise above 7.45→ alkalosis
o Alteration outside these boundaries affects all body systems
that can result in coma, cardiac failure, and circulatory collapse.
Disorders of acid-base imbalances
Disorders of acid-base imbalances
• Generally acid-base imbalances result in:
1. Metabolic acidosis
2. Metabolic alkalosis
3. Respiratory acidosis
4. Respiratory alkalosis
49
Causes :
• Starvation: ketoacidosis mostly fats burn instead of CHO
• Hypoxia: ↓O2, thus glycolysis dominates & lactic acid is generated
• Severe diaharria: large amounts of HCO3 is lost, acid dominates
Compensation : usually done through respiratory means .
a. Hyperventilation causes washout of CO2 and ↓H+ indirectly
from body fluids
H + HCO3 = H2CO3= CO2 + H2O
(the reaction goes to the right and CO2 is eliminated)
Metabolic acidosis
51
Cause: increased loss of H+ or an ↑HCO3 production in the body
a. Prolonged vomiting: HCl acid from the stomach is lost and this
effect elevates blood HCO3 level.
b. Hyper-aldosteronism: causes an increase in HCO3
reabsorption
Compensation: the respiratory system
• It inhibits respiration (causes lower breathing rate)
• Hypoventilation causes retention of CO2 and causes the pH to come
to normal
Metabolic Alkalosis
Respiratory acidosis
53
Cause - hypoventilation
• The lung fails to expire CO2 produced by metabolism.
• A lot of CO2 accumulates making the pH <7.4
a. Respiratory depression (e.g. drugs, sedatives cause hypoventilation)
b. Pulmonary diseases that cause hypoventilation (e.g. Emphysema,
asthma etc.)
Compensation - the kidney
• It increases HCO3 reabsorption that raises the pH back to normal
54
Causes:
• Excessive removal of CO2 from the body through hyperventilation.
• This causes a drop in PCO2 level in the body
• E.g. High altitude hypoxia, Anxiety, madness etc.
Compensation :
• Kidney results in a loss of HCO3 in urine until pH becomes normal
Respiratory alkalosis
A Diagnostic Chart for Acid-Base Disorders
55

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2. blood physiology

  • 2. Main blood functions • Medium of transport - Gases(O2 and Co2) - Nutrients (CHO, aa, lipids & vitamins) - Ions (Na+, Ca2+ , HCO3−) - Metabolic wastes (urea) - Hormones and enzymes • Maintains homeostasis - Body temperature regulation - PH regulation(acid-base balance) - Osmolarity and regulation of water balance • Defense - Prevents infections (WBC’s, Neutrophiles & Monocytes) 2 Introduction
  • 3. Properties of blood a. Viscosity - refers to internal resistance of a liquid to flow. - blood is 3X thicker and denser than pure water. b. Ph - normal interval is 7.35-7.45. - blood is slightly alkaline. c. Volume - 8% of total body weight. - male(5-6 Lit) and female(4-5 lit) d. Temperature - slightly warmer than body temperature e. Color - bright red (oxygenated blood) - dark red (venous blood, deoxygenated)
  • 4. Components of Blood • Blood is a connective tissue that consists of: 1. Plasma (55% or 3 Lit.): o Nonliving extracellular matrix o Fluid portion 2. Formed elements (45% or 2 Lit) o Living cells o Three types - RBC (Erythrocytes), - WBC (Leukocytes) and - Platelets (Thrombocytes)
  • 5. 5 The Haematocrit (Hct) or PCV • Un-coagulated blood is centrifuged at high speed (3000 rpm) for (5 to10 min), 3-layers form after centrifugation 1. Upper suspension - is the blood plasma accounts to about 55% of the blood volume. 2. Middle buffy coat - accounts to < 1% of the blood volume. - consists of WBC and Platelets 3. Lower portion - is a reddish mass of RBC that settles at the bottom of the test tube. - accounts to about 45% of the total bloo vol.
  • 8. • Blood plasma contains: o More than 33 different substances . o Organic molecules, water, elctrolytes, gases etc. o 8 Blood Plasma components
  • 9. Serum vs. plasma • Serum is the yellowish fluid that forms after blood is left to clot. • Serum has more or less similar composition to plasma except that its fibrinogen have been removed. So, serum is blood without fibrinogen. 9 Blood Plasma components
  • 10. 10 Plasma proteins A. Albumin (~ 60% or 4.5 gm/dl) B. Globulins ( ~ 40%, or 2.5 g/dl) C. Fibrinogen (0.3 g/dl) • Determined by means of electrophoresis Blood Plasma components
  • 12. 13 Types of blood cells: • RBCs (Erythrocytes) = 5,000,000 /mm3 • WBCs (Leucocytes) = 5,000 / mm3 • Platelets (Thrombocytes) = 200,000 / mm3 Blood Cells (Formed elements)
  • 13. 14 RBC (Erythrocytes) Properties • Biconcave shape • Non-nucleated • Diamter = 7.5 um. • Very flexible • Number =4.7-5 x106 • Develop in about 15 days • Life span is about 120 days • Produce in red bone marrow
  • 14. Hemoglobin (Hg) – red pigment of RBCs. • Functions - transports O2 & CO2 - Serves as a buffer to maintain acid-base balance. • Structure - Hg has two parts a. Globin part - 4-polypeptide chains (2alpha & 2beta globulins) b. Heme part - Porphyrin & Fe2+ at the center to w/h O2 binds. • Each polypeptide has one Heme group and each Heme contains one Fe2+ that carries 1-O2 molecule. o So, totally, 4O2 molecules are carried by 1-Hb molecule. 15 RBC (Erythrocytes)
  • 15. • Normal haemoglobin(Hg) values in the blood varies based on age. o Infants: 14 – 20 g/dl o Adult males: 13–18 g/dl o Adult females: 12–16 g/dl 16 RBC (Erythrocytes)
  • 16. RBC fragility test (hemolysis) • Fragility tests are conducted in solutions which have different tonicities. • It is conducted to determine the degree of hemolysis of RBC’s. 1.In isotonic solution - 0.9% NaCl solution is isotonic to plasma. - the size and shape of RBC remains normal 2. Hypertonic solution - greater than 0.9% NaCl solution, RBC-lose water and shrink 3. Hypotonic solution - lower than normal (<0.9%) NaCl solution, RBC hemolyse(burst) & lose their Hb to the plasma 17
  • 17. 18 Genesis of RBC’s • RBC and other blood cells are produced in the bone marrow from a single type of cells called pluripotent hematopoietic stem cells.  These cells, then differentiate and form committed stem cells that produce only specific types of blood cells. • The committed stem cells that produce : o Erythroctes - colony-forming unit–erythrocytes (CFU-E). o Granulocytes - colony forming unit granulocytes o Monocytes - colony forming unit monocytes o Platelets - colony forming unit Megakaryocytes • Lymphoid stem cells - T- and B- Lymphocytes.
  • 19. RBC and ATP production • How do RBC’s survive if they lose their nucleus and mitochondria, o which are responsible for protein synthesis and oxidative metabolism, respectively? Answer: • Mature RBC’s : Do not synthesize proteins, but utilize glucose to get energy by glycolysis • Moreover, RBC membnrane has a lot of the enzyme 2-3-DPG, which promotes release of O2 from Hb as in high altitudes 22
  • 20. Erythrocyte Sedimentation Rate (ESR) • ESR is the rate or speed at which un-coagulated blood (RBC) settles down when allowed to stand for about 1hour in a tube. • It is a non-specific test Factors that affect ESR a. Polycythemia - Hct value is large, so ESR is low b. Anemia - ESR is fast, so ESR value is high 23
  • 21. Regulation of Erythropoesis • Erythropoesis is the process of RBCs production which is egulated by -ve feed back mechanism. o Hypoxia stimulates the kidney & liver to release erythropoietin hormone ↓ o Erythropoietin reaches bone marrow throgh blood & induce stem cells to produce more RBC’s ↓ o The RBC’s release O2 to the body • So, Kidney insufficiency can cause anemia, b/s of lower synthesis of erythropoietin. 24
  • 22. 25 • Knowing the RBC-indices will help one to realize the size, Hg-level in the blood, and type of RBC abnormalities or pathologies. • Thus the 3-important facts that need to be assessed in RBC-indices includes measuring the: a. Hg-concentration b. RBC-count (No of RBCs) c. Ht (hematocrit) values RBC-indices
  • 23. RBC-indices • From the above indices, other important blood parameters can be calculated, including: 1. MCV : Mean Cell Volume 2. MCH : Mean Cell Hemoglobin 3. MCHC: Mean Cell Hemoglobin Concentration 26
  • 24. RBC indices MCV(mean cell volume): • Tells size of the RBCs a. Macrocytic • RBC that are larger or bigger in size oe.g. pernicious or megaloblastic anemia, due to Vit. 12 deficiency) b. Normocytic • RBC with normal size ~ 7 UM c. Microcytic • RBC that are smaller in size MCHC (mean cell Hg conc.) • Tells Fe status a. Normochromic • Normal Hb synthjes is 33% g/dl b. Hypochromic • Less MCHC( < 33 g/100 ml) values indicate deficient hemoglobin synt. c. Hyperchromic • High MCHC values do not occur, ob/s the Hb conc. is close to saturation point in red cells. 27
  • 25. 28 • Anemia means having decreased RBC number or lower concentration of hemoglobin (Hb) in the circulating blood. • In anemia, there is a diminished O2-carrying capacity of the blood. • Generally anemia results from excessive loss (bleeding), or destruction (hemolysis), or lower production of RBC (lack of nutrition) in the circulation. • Types of Anemia: a. Blood loss anemia b. Aplastic anemia c. Megaloblastic anemia & d. Hemolytic anemia Clinical correlates
  • 26. a. Blood loss anemia: • During hemorrhage persons loose too much blood. • The Fe2+ absorbed from the intestine is not enough to produce adequate Hgb to replace the lost Hgb that took place during bleeding. • As the result, the RBC’s produced are smaller in size and have lower Hb level causing a microcytic, hypocromic anemia. b. A plastic anemia: • Aplasia means lack of functioning bone marrow. • It is caused by exposure to excess chemicals, drugs and gamma or X- ray that destroy the bone marrow. 29 Clinical correlates
  • 27. c. Megaloblastic (pernicious) anemia • Caused by: o Nutritional deficiency: maturation failure caused by inability to absorb Vitamin-B12 and folic acid from the intestine. o Absence of intrinsic factor (gastrechtomy) is another cause. • Effect is that RBC can not proliferate properly, b/s DNA synthesis does not occur. • As the result the RBC’s become big, oversized (megaloblastic ) and have fragile membranes that easily rupture and decrease the No. 30 Clinical correlates
  • 28. d. Hemolytic anemia: hereditarily acquired and makes the RBC’s to easily rupture as they cross thru narrow blood vessels like capillaries. • Examples are: 1. Hereditary spherocytosis: spherical shaped RBC (not biconcave) that rupture easily 2. Sickle cell anemia: is caused by abnormal beta chain in Hb-structure. When exposed to low O2 (hypoxia), the Hb precipitates forming long crystals and damaging and rupturing the cell-membrane. 3. Erythroblastosis fetalis: Destruction and decrease of RBC’s number of the fetus by antibodies from Rh-negative mother. 31 Clinical correlates
  • 29. 32 • Polycethemia - high production of RBC in the circulation(7-8 m/ mm3) • It has a physiological or pathological causes. A. Physiological cause is known as secondary polycethemia : • When the tissues become hypoxic b/s of low O2-tension as in high altitude, the bone marrow produces excessive RBC (6-7 mill/mm3). B. Pathological cause is called polycethemia vera (erythremia) or primary polycythemia. • Caused mainly by genetic factors as in tumerous (cancerous) RBC production. • Moreover, increases are also seen in WBC and platelet numbers. Clinical correlates
  • 30. The pH Scale: • The pH scale is a convenient way of designating the concentrations of H+ and OH- in solution in the range between 1.0 M H+ and 1.0 M OH-. • PH is the (-) logarithm of [H+] where as POH is the (-) log of [OH] PH = -log [H ]; POH = -log [OH-]. o Solutions in w/c [H+] = [OH-] are neutral and have PH values = 7.0 o Solutions in which [H+] > [OH-] are acidic and have pH values ˂ 7.0. o Solutions in which [H+] < [OH-] are basic and have pH values ˃ 7.0. PH and Regulation of acid-base balance
  • 31. • PH of the body fluids (acid-base balance ) is regulated by 3 important ways. A. The buffer system (chemical buffers) B. The respiratory system (CO2) C. The renal system ( HCO3) 34 PH and Regulations of acid-base balance
  • 32. • Buffers are aqueous systems that tend to resist changes in pH o when small amounts of strong acid [H+] or base [OH-] are added. • A buffer system consists of a weak acid (the proton donor) and its conjugate base (the proton acceptor). • Because buffer systems have both HA and A- species, they are capable of absorbing either strong base or strong acid • E.g. a mixture of equal concentrations of acetic acid and acetate ion is a buffer system. A. The Buffer System
  • 33. • Strong acids (HCl and H2SO4 ) strong bases (NaOH and KOH )are are complately ionized in aqueous solutions. HCl  H+ + Cl- (strong acid) NaOH  Na+ + OH- (strong base) • Weak acids(acetic acid, lactic acid, carbonic acids) and weak bases (MgOH, AlOH)are not completely ionized when dissolved in water. o Instead, depending upon the pH, both the proton donor species (conjugate acid) and proton acceptor species (the conjugate base) occur together in solution. A. The Buffer System
  • 34. • Each weak acid has a characteristic tendency to lose its proton in aqueous solution. HA H+ + A- • PH of the buffers is calculated by the Henderson-Hasselbach equation. • PH = pKa+ log Conjugate base = pKa + log [A-] / [HA] Weak acid Ka – equilibrium constant
  • 35. A. The Buffer System • There are 4-types of chemical buffers, w/c are intracellular (ICF) and extracellular (ECF) • These are: 1. Bicarbonate/carbonic acid buffer system(ECF) 2. Protein buffer system (ICF or ECF) 3. Hemoglobin buffer system (ICF) 4. Phosphate buffer system (ICF) 38
  • 36. A. The Buffer System
  • 37. 1. Bicarbonate/carbonic acid buffer system • The most important buffer of the plasma is the bicarbonate/ carbonic acid buffer system • The ratio of base to acid (HCO3-/H2CO3) is nearly 20/1 in plasma under physiological conditions o i.e. HCO3 -/H2CO3 = 20/1, when plasma pH=7.4 • This buffer system is more complex than others, o Because carbonic acid (H2CO3) is formed from dissolved CO2 which produced in tissues and diffused to plasma.
  • 38. CO2 + H2O H2CO3 HCO3 - + H+ • This reaction is slow in plasma but in erythrocytes, carbonic anhydrase increases the rate of this reaction. • When hydrogen ion concentration increases in plasma, HCO3 - ions bind to H+ forming H2CO3. o H2CO3 is dissociated to CO2 + H2O o The extra CO2 is then released to the atmosphere by lungs 1. Bicarbonate/carbonic acid buffer system
  • 39. 2. Protein buffer system • If pH climbs, the carboxyl group of amino acid acts as a weak acid • If the pH drops, the amino group acts as a weak base • Proteins are much more effective buffers in intracellular medium. • Buffering effect of proteins is low in plasma o Proteins, especially albumin, accounts for 95% of the non- bicarbonate buffer value of the plasma.
  • 41. 3. Hemoglobin buffer system • Prevents pH changes when PCO2 is rising or falling • Hemoglobin (Hg) is a protein which carries O2 to tissues and CO2 from tissues to lungs and is an effective buffer. • Around 95% of CO2 released from tissues to plasma is diffused into erythrocytes.
  • 42. • In erythrocytes, carbonic anhydrase catalyzes the formation of H2CO3 from CO2 and H2O which in turn dissociates to HCO3 - & H+. Carbonic anhydrase • CO2 + H2O H2CO3 HCO3 - + H+ • Released protons take part in the formation of salt bridges between globin chains of Hb, and lead the change in the conformation of Hb molecule in tissue capillaries. 2. Hemoglobin buffer system
  • 43. 4. The Phosphate buffer system • Phosphate buffer system is most effective in intracellular medium, especially in kidneys. • Phosphate buffer system is not effective in plasma, because phosphate ion concentrations are low. • However it is important in the excretion of acids in the urine. o H+ secrected into the tubular lumen by the Na+–K+ exchanger react with HPO4 2- to form H2PO4 -. • Some organic phosphates (2,3 diphosphoglycerate in erythrocytes) has also buffering capacity.
  • 44. • The pH of the ECF remains between 7.35 and 7.45 o If plasma level: - fall below 7.35 → acidosis - rise above 7.45→ alkalosis o Alteration outside these boundaries affects all body systems that can result in coma, cardiac failure, and circulatory collapse. Disorders of acid-base imbalances
  • 45. Disorders of acid-base imbalances • Generally acid-base imbalances result in: 1. Metabolic acidosis 2. Metabolic alkalosis 3. Respiratory acidosis 4. Respiratory alkalosis
  • 46. 49 Causes : • Starvation: ketoacidosis mostly fats burn instead of CHO • Hypoxia: ↓O2, thus glycolysis dominates & lactic acid is generated • Severe diaharria: large amounts of HCO3 is lost, acid dominates Compensation : usually done through respiratory means . a. Hyperventilation causes washout of CO2 and ↓H+ indirectly from body fluids H + HCO3 = H2CO3= CO2 + H2O (the reaction goes to the right and CO2 is eliminated) Metabolic acidosis
  • 47. 51 Cause: increased loss of H+ or an ↑HCO3 production in the body a. Prolonged vomiting: HCl acid from the stomach is lost and this effect elevates blood HCO3 level. b. Hyper-aldosteronism: causes an increase in HCO3 reabsorption Compensation: the respiratory system • It inhibits respiration (causes lower breathing rate) • Hypoventilation causes retention of CO2 and causes the pH to come to normal Metabolic Alkalosis
  • 48. Respiratory acidosis 53 Cause - hypoventilation • The lung fails to expire CO2 produced by metabolism. • A lot of CO2 accumulates making the pH <7.4 a. Respiratory depression (e.g. drugs, sedatives cause hypoventilation) b. Pulmonary diseases that cause hypoventilation (e.g. Emphysema, asthma etc.) Compensation - the kidney • It increases HCO3 reabsorption that raises the pH back to normal
  • 49. 54 Causes: • Excessive removal of CO2 from the body through hyperventilation. • This causes a drop in PCO2 level in the body • E.g. High altitude hypoxia, Anxiety, madness etc. Compensation : • Kidney results in a loss of HCO3 in urine until pH becomes normal Respiratory alkalosis
  • 50. A Diagnostic Chart for Acid-Base Disorders 55