Blood Physiology Flashcards
Body fluids are what percentage of body weight
70%
What is the percentage of ECF
45
What is the percentage of ICF
55
What are examples of ECF
Lymph, vitreous humour ,endolymph, perilymph, synovial fluid, CSF, Aqueous humour, pleural, pericardial and peritoneal fluid
Out of total body mass, males are
40% solids, 60% fluids
Females are 45% solids, 55% fluids
List the physiological variations of body fluids
Age, Sex, Altitude, Muscular exercise, Pregnancy, Drugs
An obese has body fluids of
40-45%
How is Age a physiological variation of body fluids
When babies are born they are 80% fluids, however as the baby grows the composition decreases. That’s why loss of fluids is more drastic in babies.
How is sex a physiological variation of body fluids
There is a higher volume in males than females
How does Altitude affect body fluids
People living at higher altitudes have higher blood volumes due to relative hypoxia.
How does Muscular exercise affect body fluids
Higher muscular output means more cardiac output and thus more blood
How does pregnancy affect blood volume
Pregnant women have more blood volume, RBCs too
How do drugs affect blood volume
Certain drugs like steroids increase blood volume
What are the non physiological factors that affect blood volume (increase)
Congestive cardiac volume
Renal failure
Liver failure
Over infusion of intravenous fluids
Hypothyroidism
Adrenal gland failure
What separates ICF from surrounding ISF
Plasma membrane
What separates ISF from plasma
Blood vessel wall
What factors cause a decrease of blood volume
Dehydration
Hemorrhage
Anaemia
Shock
What could cause dehydration
Diarrhoea, Excessive vomiting, intercutaneous fistula(abnormal connection between intestine and skin)
Scalding and burns
Polyuria
Heat stress of heat stroke
What are the organic components of body fluids
Glucose,
Amino acids
Hormones
Enzymes
Fatty acids
What are the inorganic substances of body fluids
Sodium
Calcium
Magnesium
Potassium
Chloride
Sulphate
Phosphate
What is th most abundant cation of the ECF
Sodium.
What is the most abundant anion in ECF
chloride
What are the functions of Sodium in ECF
Muscle contractions
Impulse transmission
Fluid and electrolyte balance
What are the functions of chloride in ICF
forms HCL in gastric acid
Regulates osmotic pressure
What is the most abundant cation in ICF
Potassium
What are the functions of potassium in ICF
Resting membrane potential, action potential, maintenance of ICF volume, regulation of pH (by exchanging for H+)
What are the anions in the ICF
Proteins and phosphates (HPO4 2-)
What is the second most prevalent anion in ECF
Bicarbonate
What are the functions of bicarbonate in ICF
Conc. Increases as blood passes through the capillaries, generating CO2
Chloride shift helps maintain balance of anions between ICF and ECF
What is the composition of Magnesium in ICF AND ECF
45% ICF, 1% ECF
What is the second most abundant cation in ICF
Magnesium
What is the function of Magnesium
Cofactor for several enzymes and sodium potassium pump.
Essential for synaptic transmission normal neurocardial function and myocardial function.
What is lymph?
A clear colourless fluid made of 96% water and 4% solids.
What are the solids that make up lymph
a. proteins: 2-6% of solids, they are: albumin,globulin,fibrinogen, prothrombin,clotting factors,antibodies and enzymes
b. Lipids: 5-15% of solids, they are Chylomicrons and Lipoproteins
c. Carbs: glucose
d. NPN: Urea and creatinine
e. Electrolyte: sodium,calcium,potassium,chloride,bicarbonate
What are the functions of lymph
1.Return of proteins from tissues to blood
2.Redistribution of fluid from the blood
3.Removal of bacteria,toxins and other foreign bodies
4.Maintenance of structural integrity of tissue
5.Transport of lymphocytes
6.Routes for intestinal fat absorption
What is Milk, Asin describe it with its % composition
83 to 87% water and 13 to 17% solids
What are the solid components of milk
CARBS: Lactose
LIPIDS: Triacylglycerols, palmitic acid, myrstic acid, stearic acid, butyric acid, oleic acid.
PROTEINS: Caesin(80%), Enzymes(proteases,xanthine oxidase, lysozyme)
Immunoglobulins
MINERAL: calcium, magnesium, phosphorus, sodium, chloride
VITAMINS: fat and water soluble vitamins except vitamin C
What are the functions of milk
It makes galactose a structural unit for a growing Infant.
Lactic acid in the intestine kills germs
It is a source of proteins, minerals and vitamins
Describe Amniotic fluid
It is produced by membranes and the foetus. It’s volume increases with gestational age. It is clear with some desquamated fetal cell and a small amount of lipids.
What are the functions of Amniotic fluid
Protects fetus
Medium of exchange of materials btwn mother and child
Describe the aqueous humor
It fills the anterior chamber of the eye and is secreted by the ciliary body.
What is a clinical correlate of the aqueous humor
It causes glaucoma due to increased intraocular pressure
Perspiration of sweat is how many litres a day
800- 1200mL
Sweat is secreted from wetin
The sweat glands
Sweat electrolytes are controlled by what
By ANS (adrenal cortical steroid)
In exercise or high temps, what could happen to sweat
sweat can be 10-14L, which may cause Electrolyte imbalance.
What is the pH of sweat
4.7-7.5
What are the electrolyte components of sweat
Sodium= 12.6-127meq/L
Potassium= 5-32 meq/L
Chloride= 8.5-85 meq/L
Describe tears
They are isotonic fluids secreted by the lacrimal gland
When are tears isotonic and hypertonic
They are isotonic normally and when they pass over the eye in large amounts. They are hypertonic when they pass over the eye in small amounts.
What is the protein content of tears
0.6 to 0.18g/dL, with and albumin/globulin ratio of 1:5 or 2:1.
And a small amount of mucin
What is the Ph of tears
7-7.6.
What is the function of lysosome in tears
Breaking down the polysaccharides in their outer layer
List the functions of tears
Protect the eye from infection
Lubticates the surface of the cornea
Fill the irregularities of the cornea
Protects the eye from injury
What is the body water content of infants
73-80% I.e low fat, body mass
What is the body water content of adult males
50-60%
What is the body water content of adult females
40-50%
What is the body water content in old age
45%
What is the ideal water intake
2500mL/day
What are the various forms of water output
Urine(60%), insensible water loss from skin and lungs, perspiration and feaces
What is osmolality
Osmolality is a measure of the concentration of dissolved particles such as salt or sugar in a solution. it is defined as the number of osmoles of solute per kilogram of solvent.
An osmole is the number of particles that contribute to the osmotic pressure of a solution.
What will increased osmolality do
Simulates thirst
ADH release
What will decreased osmolality do
Thirst inhibition
ADH inhibition
What is osmotic pressure
The force that causes water to move from areas of low solute concentration to areas of high solute concentration across a semi permeable membrane.
What factors cause ADH release
Low blood pressure
Factors like diarrhoea, fever, burns, hemorrhage, that reduce blood volume
What are the disorders of water balance
Dehydration,
hypertonic hydration
edema
What is used to treat hypotonic hydration
Hypertonic saline
What is the indicator criteria for measuring plasma
It must not cross the capillaries
What are the indicators for plasma
Evans blue dye, Radioactive iodine, radioiodinate fibrinogen, radioiodinated albumin
What is the criteria for using an indicator on ECF volume
it can cross capillaries but not cell membrane
What is the indicator criteria for measuring the total body water
It should distribute evenly between ECF and ICF
What are the indicators for ECF
Isotonic solutions of sucrose, NaCl, Inulin, Mannitol.
What are the indicators of total body fluid
Heavy water, titrated water, antipyrine and aminopyrine
What are the methods of measuring total body water
Indirect method: indicators I.e dye dilution technique(the law of mass conservation)
What is the principle of indicator dye dilution technique
A well mixed substance should only be present itself at the compartment of interest
State the formulas to measure the volume of fluid by indicator dilution method
Concentration= to amount injected /volume of distribution
Amount of matter remained in a compartment is = amount of marker added - amount of marker lost from the compartment.
Therefore,
compartment volume = amount of marker added - amount of marker lost from the compartment / concentration of marker
So what are the criteria of a simple dye
It must be mixed evenly throughout the compartment
It must have no physiological change
It must be easy to measure
It must be unchanged, or the amount changed should be known
How is ICF measured
ICF= Total body water- ECF volume
How is ISF measured
ISF = ECFV - PV
How do the plasma proteins control body fluid volumes
Proteins in plasma(colloids) cause pressure (osmotic pressure) that forces fluid from Interstitial spaces to blood.
What is a colloid
A non crystalline chemical that is insoluble in water, and unable to pass through a semipermeable membrane, but it’s diffusible
What are the ways body fluids concentration is expressed
Osmolality
Osmolarity
Tonicity
Explain osmolarity
It’s the term for osmotic concentration, it is the number of osmoles per litre of a solution. The unit is osmoles/L.
Even though osmotic pressure is dependent on osmolality, osmolarity in practice is used to calculate osmotic pressure.
Why is osmolarity instead of osmolality used to calculate osmotic pressure
A. the measurement of weight in water is a difficult process.
B. The difference between osmolality and osmolarity is negligible and thus could be used interchangeably
What is the difference between osmolality and osmolarity
A. OSMOLALITY is the concentration of a solution expressed as the total number of solute particles per kilogram.
While…
OSMOLARITY is the concentration of a solution expressed as osmoles of solute particles per litre of solution.
B. OSMOLALITY is calculated considering mass of solution
While…
OSMOLARITY is calculated considering volume of solutio
C. OSMOLALITY unit is osmol/L
While…
OSMOLARITY unit is mol/L
D. OSMOLALITY does not depend on temp and pressure
OSMOLARITY depend on temp and pressure
What happens when osmolality of ECF increases
Water flows from ICF to ECF
What happens when osmolality of ECF decrease
Water flows from ECF to ICF
What is Tonicity, add the explanation of effective osmolality to complete the definition
Tonicity is a measure of effective osmolality.
Explain effective osmolality
The movement of water across fluid compartments is not influenced by small molecules like Urea and alcohol, those pass rapidly.
On the contrary, molecules like glucose and sodium take time, due to their sizes and thus… Influence the flow of water.
The osmolality that causes the movement of water between components is EFFECTIVE OSMOLALITY.
Wtf is the difference between ISF and Plasma
Plasma contains more proteins than ISF
What are the significances of body fluids
Homeostasis,
Transport mechanism,
Metabolic reactions,
Aqeous humor,
The characteristics and texture of a tissue is controlled by ICF,
Temperature regulation,
They are essential for diffusion and filteration,
They are an ionising medium for regulating pH and Osmolality,
They line cavities and lubricate surfaces of joints,
CSF is a mechanical buffer that acts as a shock absorber for the brain and spinal cord.
Korede could you introduce blood for me? Like what tf do you see blood as?
Blood is a connective tissue, red in colour. It is Scarlet red when oxygenated in the arteries and Violet red when deoxygenated. The main function of the blood is transport. Transport of nutrients, waste products, hormones, and other substances from the places they were released to where they are needed.
The properties of blood are: colour, volume, reaction and pH, specific gravity, viscosity, % body weight.
The composition of blood: the blood cells and the liquid component- plasma
Explain the color property of blood.
COLOR: blood is red in colour, Arterial blood is scarlet red because it contains more oxygen and venous blood is purple red because of more carbondioxide.
explain the volume ppt of blood
VOLUME: in a newborn baby it is 450mL
In male it is 5-6mL
In female it is 4-5mL
It is typically 8% body weight in a normal human being i.e of 70kg. therefore in a person of 70kg, blood consists 4.9kg
explain the reaction and pH of blood
blood is slightly alkaline with a pH of 7.4
explain the specific gravity of blood
Specific gravity of total blood : 1.052 to 1.061
Specific gravity blood cells : 1.092 to 1.101
Specific gravity of plasma : 1.022 to 1.026
what is the viscosity of blood
blood is 5X more viscous than water. this is due to the RBC and plasma proteins
what is the osmolarity of blood
280 – 296mosm/l.
what are the functions of blood
Transportation of substances
Regulation of temperature and blood level of substances
Protection or defence of the body against infections
explain the transportation of substances function of blood
- Blood carries O2 from the lungs to the tissues and CO2 from tissues to the lungs in the body. This is also known as respiration function of the blood.
- Blood transports nutritive substances like glucose, amino acids, lipids and vitamins derived from digested food from the gastrointestinal tract, to different tissues in the body.
- Blood transport hormones secreted by endocrine glands to the their target organs or tissue.
- Blood also transport enzymes.
5.Blood carried waste to liver, skin and kidneys for detoxification or removal.
explain the ‘Regulation of temperature and blood level of substances’ function of blood
- Blood regulate body temperature by absorbing and distributing heat, thereby maintaining the thermoregulating mechanism in the body.
- Blood regulate water content of the body. The content of the blood is freely interchangeable with interstitial fluid, this brings about the stability in water balance in the body.
- Blood regulate acid base balance in the body through the plasma proteins and haemoglobin which acts as buffer,
- Water and important substances like proteins, glucose, Na+, K+ are stored in the blood.
explain the ‘Protection or defense of the body’ function of blood.
1.The blood play a role in inflammation,
2.The WBC destroy microorganisms and cancer cells, preventing infections,
3.Antibodies and compliments neutralize or destroy pathogens.
4.Platelets and clotting factors initiate clotting and minimize blood loss.
what is plasma
Plasma is a straw-colored clear liquid part of blood. It contains 91% to 92% of water and 8% to 9% of solids. The solids are the organic and the inorganic substances
what are the organic substances in plasma
glucose, amino acids, lipid, cholesterol, vitamins, enzymes hormones, plasma proteins.
what are the inorganic substances in plasma
trace elements, O2, CO2, Na+, K+, Cl–
what are the sites of production of the plasma proteins
Liver, spleen, bone marrow and B-lymphocytes.
what are the plasma proteins and thier respective compositions
albumin-60%
Globulin- 36%
Fibrinogen- 4%
Using a diagram of the hematocrit, describe the components of plasma
check drawing 11 in booklet.
what is the specific gravity of plasma
1.022-1.026
what are the molecular weights of the various plasma proteins
Albumin : 69,000
Globulin : 156,000
Fibrinogen : 400,000
what is the composite volume of the plasma proteins
Total proteins : 7.3 g/dL (6.4 to 8.3 g/dL)
Serum albumin : 4.7 g/dL
Serum globulin : 2.3 g/dL
Fibrinogen : 0.3 g/dL
what is the function of the plasma proteins
Albumin: Helps to maintain osmotic pressure
Globulin: Transport of lipids and fat soluble substances
Fibrinogen: participates in blood clotting
what is the A/G ratio
The ratio between plasma level of albumin and globulin is called albumin/globulin (A/G) ratio. It is important indicator of some diseases involving liver or kidney. The normal value is 2:1
what are the functions of plasma proteins
- transportation
2.Osmoregulation - The role in defense mechanism of the body
- Role in coagulation:
- Regulation of acid base balance
- Viscosity of the blood
7.Suspension stability of the red blood cells
explain the ‘transportation’ function of plasma proteins
TRANSPORTATION: Plasma proteins are essential for the transport of various substances in the blood:
-Transferrin transports iron
-Ceruloplasmin transport copper
-Albumin transports fatty acids, bilirubin, calcium many drugs etc.
-Transcortin transports cortisol and corticosterome
-Lipoproteins transports lipids
-Haemoglobin transports free haemoglobin
-Alpha and beta globulins transport substances such as iron, copper, and lipids
explain the ‘osmoregulation’ function of plasma proteins
plasma proteins are colloidal and non-diffusible and exert a colloidal osmotic pressure which helps to maintain a normal blood volume and water content in the interstitial fluid and tissues. Albumin content regulates colloidal osmotic or oncotic pressure/osmotic pressure.
Osmotic pressure exerted by plasma proteins play an important role in the exchange of various substances between blood and the cells through capillary membrane. as seen from starlings hypothesis
what is starlings hypothesis
The net filtration through capillary membrane is proportional to the hydrostatic pressure difference across the membrane minus the oncotic pressure difference
explain the ‘The role in defense mechanism of the body’ function of plasma proteins
The plasma proteins particularly the gamma globulins plays a important role in the defense mechanisms of the body by acting as antibodies (Imminoglobulins). The reaction of the antibodies to antigens of various microorganisms prevents the body against infections. The Igs and compliments protects the body against foreign bodies and remove damaged tissues.
explain the ‘Role in coagulation’ function of plasma proteins
fibrinogen and other clotting factors found in plasma is essential for the coagulation of blood.
explain the ‘Regulation of acid base balance’
plasma proteins particularly the albumin are important in regulating the acid base balance in the blood because of their buffering action.
explain the ‘viscosity of blood’ function of plasma proteins.
the plasma proteins provide viscosity to the blood which is important for maintaining the blood pressure.
explain the ‘Suspension stability of the red blood cells’ function of plasma proteins.
the globulin and fibrinogen helps in suspension stability of the red blood cells during circulation. Globulin and fibrinogen also accelerate rouleaux formation by the red blood cells.
You are now writing an essay on RBC, Introduce the RBC
The RBC also known as erythrocytes are biconcave disc, anucleate, essentially has no organelles. Red color of the RBC is due to the presence of the coloring pigment
called hemoglobin. RBCs play a vital role in transport of respiratory gases. RBCs are larger in number compared to the other two blood cells, namely white blood cells and platelets.
You are now writing an essay on RBC, write on it’s normal value
RBC count ranges between 4 and 5.5 million/cu mm of blood. In adult males, it is 5 million/cu mm and in adult females, it is 4.5 million/cu mm.
RBC count in males is
5 million/cu mm- 5.5 million/cu mm
RBC count in females is
4.5 million/cu mm- 5 million/cu mm
You are now writing an essay on RBC, write on it’s morphology[SHAPE]
RBCs are disk shaped and biconcave (dumbbell shaped). Central portion is thinner and periphery is thicker. The biconcave contour of RBCs has some mechanical and functional advantages:
-Helps in equal and rapid diffusion of oxygen and other substances into the nterior of the cell.
-Large surface area is provided for absorption or removal of different substances.
-Minimal tension is offered on the membrane when the volume of cell alters.
-Because of biconcave shape, while passing through minute capillaries, RBCs squeeze through the capillaries very easily without getting damaged.
You are now writing an essay on RBC, write on it’s morphology[SIZE]
Diameter : 7.2 µ (6.9 to 7.4 µ).
Thickness : At the periphery it is thicker with 2.2 µ and at the center it is thinner with 1 µ because of the biconcave shape.
Surface area : 120 sq µ.
Volume : 85 to 90 cu µ.
Draw a diagram to explain your writings on the morphology of the RBC
Check drawing 12, booklet
You are now writing an essay on RBC, write on it’s morphology[STRUCTURE]
Due to the absence of nucleus in human RBC, the DNA is also absent. Other organelles such as mitochondria and Golgi apparatus also are absent in RBC. Because of absence of mitochondria, the energy is produced from glycolytic process. Red cell does not have insulin receptor and so the glucose uptake by this cell is not controlled by insulin. The cell also has a network of actin and spectrin which act as a cytoskeleton to anchor the inner parts of the surface glycoproteins and maintain the shape of the cell.
Why is RBC larger in venous blood
As a result of osmotic changes, and the consequent passage of water into the RBC through the cell membrane, the diameter increases with a shift in the acid-base balance of the blood toward the acid side. The RBC are therefore more slightly larger in venous than in arterial blood.
What is contained in the RBC stroma
The stroma of RBC contains lipids, insoluble proteins and cholesterol, the antigenic nature of the erythrocyte appears to be a property associated with the stroma. Hb makes up about 30 to 34% of wet weight of Red Blood Cell and 95 to 98% of dry weight of Red Blood Cell. RBC also contains the enzymes of the glycolytic system- catalase and carbonic anlydrase, all of the glutathione of the blood as well as other enzymes and organic and inorganic salts. Potassium is present in high concentration in RBC, relative to sodium.
what % of Hb constitutes dry weight of rbc
95-98%
what % of Hb constitutes wet weight of rbc
30-34%
You are still writing an essay on RBC, what are their properties
-Rouleaux formation: when anti coagulated blood sample is allow to stand for a period of time, the RBC pule up one above the other and settles at the botton of the tube. This property of the RBC is called rouleaux formation.
-Packed Cell Volume (PCV): When anticoagulated blood centrifuged for a period of time. The RBC settle down leaving a clear plasma at the top. The RBC for 45% of the total blood and the volume of plasma 55%. This is called the packed cell volume or haematocrit.
-Specific gravity: 1.092 to 1.101
-Agglutination: RBC, carry blood group antigens (Anti A, B, AB, Rh factors). The reaction between antigen and antibody result in agglutination.
You are writing an essay on RBC, what is the life span
Average lifespan of RBC is about 120 days. After the lifetime the senile (old) RBCs are destroyed in reticuloendothelial system.
You are writing an essay on RBC, what are the physiological variations (that increase RBC count)
Increase in the RBC count is known as polycythemia, when it occurs due to physiological conditions, it is physiological polycythemia:
-Age: At birth, the RBC count is 8 to 10 million/cu mm of blood. The count decreases within 10 days after birth due to destruction of RBCs causing physiological jaundice in some newborn babies. In adults it ranges between 4 and 5.5 million/cu mm
-Sex: Before puberty and after menopause in females the RBC count is similar to that in males. During reproductive period of females, the count is less than that of males (4.5 million/cu mm).
-High altitude: Inhabitants of mountains (above 10,000 feet from mean sea level) have an increased RBC count of more than 7 million/cu mm. It is due to hypoxia (decreased oxygen supply to tissues) in high altitude. Hypoxia stimulates
kidney to secrete a hormone called erythropoietin that causes increased production of RBC.
-Muscular exercise: There is a temporary increase in RBC count after exercise. It is because of mild hypoxia and contraction of spleen. Spleen stores RBCs. Hypoxia
increases the sympathetic activity resulting in secretionof adrenaline from adrenal medulla. Adrenaline contracts spleen and RBCs are released into blood —Emotional conditions: RBC count increases during the emotional conditions
such as anxiety. It is because of increase in the sympathetic activity.
-Increased environmental temperature: Increase in atmospheric temperature increases RBC count. Generally increased temperature increases all the activities in the body including production of RBCs.
-After meals: There is a slight increase in the RBC count after taking meals. It is because of need for more oxygen for metabolic activities.
You are writing an essay on RBC, what are the physiological variations (that decrease RBC count)
- High barometric pressures: At high barometric pressures as in deep sea, when
the oxygen tension of blood is higher, the RBC count decreases. - During sleep: RBC count decreases slightly during sleep and immediately after getting up from sleep.
- Pregnancy: It is because of increase in ECF volume. Increase in ECF volume,
increases the plasma volume also resulting in hemodilution. So, there is a relative reduction in the RBC count.
What is the specific gravity of RBC
Specific gravity: 1.092 to 1.101
what are pathological factors that increase RBC count
Polycythemia vera – this is a pathological condition in which the red blood cell count and PCI is high. Polycythemia vera is caused by genetic aberration in the haemocytoblastic cells. The viscosity of the blood in polycythemia vera is increase 10 times that of water.
Anemia.
What is haemotopoiesis
Haemopoiesis or haemotopoiesis is the process of formation of new blood cellular components. It has been estimated that in an adult human, approximately 10^11 – 10^12 new blood cell are produced daily in order to maintain steady state level in the peripheral circulation.
Describe the different sites of haemotopoiesis in human life
In human embryo, the first detectable precursors of blood cells are found in the yolk sac.
By the third month of fetal life, however, the processes of blood cell formation (haemotopoiesis) predominantly occur in the liver.
By the fourth and fifth month, haemotopoiesis commences in the bone marrow where it is fully active by the seventh to eight month, and
At birth practically the whole bony skeleton contains active marrow.
During the childhood and adolescence there is a market recession of marrow activity in the long bone so that in the adult activity is limited to truncal skeleton and skull, only a little remaining in the proximal ends of humeral and formural shafts.
In adult, the marrow normally consists of islands of cellular active marrow separated and support by fat. After the age of 50 years the proportion of active marrow declines somewhat, that of the fat increasing.
what are Hematopoietic stem cells
Hemopoietic stem cells are the primitive cells in the bone marrow, which give rise to the blood cells. Hemopoietic stem cells in the bone marrow are called uncommitted pluripotent hemopoietic stem cells (PHSC). PHSC is defined as a cell that can give rise to all types of
blood cells. In early stages, the PHSC are not designed to form a particular type of blood cell. And it is also not possible to determine the blood cell to be developed from these cells: hence, the name uncommitted PHSC
In adults, only a few number of these cells are present. But the best source of these cells is the
umbilical cord blood.
When the cells are designed to form a particular type of blood cell, the uncommitted PHSCs are called committed PHSCs. Committed PHSC is defined as a cell, which is restricted to give rise to one group of blood cells
what are the 2 types of committed hematopoietic stem cells
-Lymphoid stem cells which give rise to lymphocytes and natural killer (NK) cells.
-Colony forming blastocytes which give rise to myeloid cells
What are the types of colony forming blastocytes
-Colony forming unit – erythrocytes (CFU – E) this give rise to erythrocytes
-Colony forming unit – Granulocytes/monocytes (CFU – GM) this give rise to neutrophils, eosinophils, monocytes and basophils.
-Colony forming unit – Megakaryocytes (CFU – M) this give rise to platelets.
What are hematopoietic growth factors
Haemopoietic growth factors are glycoprotein hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells and function of mature blood cells.
What are examples of hematopoietic growth factors
Erythropoietin,
Thrombopoietin colony-forming stimulating factor granulocyte (GCSF),
Macrophage colony-stimulating factor (M – CSF)
Cytokines (IL3, 5, 6 & 11)
What is Erythropoiesis
The production of RBC occurs in the bone marrow and is a complex, regulated process for maintaining adequate numbers of erythrocytes in the peripheral blood. Erythropoiesis is the process which involves the origin development and maturation of erythrocytes.
What are the processes of Erythropoiesis
Proerythroblast, Early normoblast, Intermediate normoblast, late normoblast, Reticulocyte
What is to be said about the proerythroblast stage of Erythropoiesis
It’s a very large cell 20µM in diameter. The nucleus occupies the cell completely(large nucleus) with multiple nucleoli and a reticular network. This cell does not contain haemoglobin. The cytoplasm is basophilic. The proerythroblast multiplies several times to form the early normoblast.
What can you say about the early normoblast stage of Erythropoiesis
has a diameter of 15µm. The nucleoli of the nucleus disappears. Condensation of chromatin network occurs cytoplasm is basophilic in nature. There is little or no haemoglobin in this cell.
what can you say about intermediate normoblast stage of Erythropoiesis
this cell is 10 to 12µ in diameter. The chromatin network condense further. Though the nucleus is still present, the haemoglobin starts appearing. The cytoplasm is basophilic. It stains both acidic and basic stains and is referred to as polychromophilic.
what can you say about intermediate normoblast stage of Erythropoiesis
this cell is 8 to 10µ in diameter. There is a small nucleus and a very much condense chromatin network present. The quantity of haemoglobin increases and the cytoplasm becomes almost acidophilic (arthochromic erythroblast). The nucleus later disintegrates and disappears (phyknosis).
what can be said about Reticulocyte stage of Erythropoiesis
This is an immature RBC. It is larger than a mature RBC. The cytoplasm contains the remain of the reticular network. The normal value in the blood is 2 to 6%. The number increases value when production and release of RBC increases. Recticulocyte is basophilic due to the remaining of golgi apparatus, mitochondria and other organelles in the cytoplasm.
Comment on how red blood cells are regulated
The rate of RBC production equals its destruction, this is because of a hormone called erythropoietin.
Comment on erythropoietin
Erythropoietin is is a polycoprotein hormone (M, 33000), which is normally present in plasma at low concentration (about 10mmol/L) and with a half-life of about 5 hours with 165 amino acids. Erythropoietin is secreted mostly by the kidney (90%) and the liver (10%) and the brain in response to local hypoxia. The hormone acts on the red marrow to cause the increased output of erythrocytes until the rise of haemoglobin concentration of the blood restores normal delivery of O2 to the tissues.
what are the factors needed for erythropoiesis grouped into
they are grouped into
- general factors
-maturation factors
-factors necessary for Hb formation
what are the general factors needed for erythropoiesis
-Erythropoietin
-thyroxine
-hemapoietic growth factors
-vitamins
comment on thyroxine (on the stimulation of erythropoiesis)
Being a general metabolic hormone, thyroxine
accelerates the process of erythropoiesis at many levels. So, hyperthyroidism and polycythemia are common.
comment on vitamins (as a stimulant for erythropoiesis)
Vitamins B,C,D,E in absence may cause anemia or related disorders
comment on hematopoietic growth factors
These factors induce the proliferation of PHSCs.
Interleukins (IL) are glycoproteins, which belong to the cytokines family.
Interleukins involved in erythropoiesis:
a. Interleukin-3 (IL-3) secreted by T-cells
b. Interleukin-6 (IL-6) secreted by T-cells,endothelial cells and macrophages
c. Interleukin-11 (IL-11) secreted by osteoblast
what are the maturation factors of erythropoiesis
Vitamin B12
Intrinsic factor of castle
Folic acid
Comment on vitamin B12 as a maturation factor
Vitamin B12 is an extrinsic factor since its obtained from diet. It’s absorbtion in the intestine requires intrinsic factor of castle. It is store in the Liver, and in muscle (in small amounts)
It is responsible for DNA synthesis in the RBC, it’s deficiency causes large RBC with weak cell membranes, i.e macrocytic anemia.
Deficiency of B12 causes pernicious anemia.
Comment on intrinsic factor of castle as a maturation factor of RBC
It is produced in the gastric mucosa by the parietal cells of the gastric glands. It is responsible for the absorption of B12 through the intestinal walls. Therefore, a deficiency of intrinsic factor of castle would cause pernicious anemia.
Deficiency of intrinsic factor occurs in:
i. Severe gastritis
ii. Ulcer
iii. Gastrectomy.
comment on folic acid as a maturation factor of RBC
Folic acid is also essential for maturation. It is required for the synthesis of DNA. In the absence of folic acid, the synthesis of DNA decreases causing failure of maturation. This leads to anemia in which the cells are larger and appear in megaloblastic (proerythroblastic) stage. And, anemia due to folic acid deficiency is called megaloblastic anemia.
What are the factors necessary for Hb production
-First class proteins and AMINO acids
-Iron
-Copper
-Cobalt and Nickel
-Vitamins
comment on the role First class proteins and amino acids play in Hb production
Proteins of high biological value are essential for the formation of hmoglobin. Amino acids derived from these
proteins are required for the synthesis of protein part of hemoglobin, i.e. the globin.
role of iron in Hb synthesis
Necessary for the formation of heme part of the hemoglobin.
role of Copper in Hb synthesis
Necessary for the absorption of iron from the gastrointestinal tract
role of cobalt and Nickel in Hb synthesis
These metals are essential for the utilization of iron during hemoglobin formation.
role of vitamins in Hb synthesis
Vitamin C, riboflavin, nicotinic acid and pyridoxine are also essential for the formation of hemoglobin.
molecular weight of Hb
68000
Hb forms what percentage of dry weight of RBC
95%
Hb forms what percentage of wet weight of RBC
30-34%
what are the globin chains in Hb
2α- and 2β-
how many amino acids are in the α- chains
141
how many amino acids are in the β chains
146
what is the Hb content level (generally)
14 to 16 g/dL.
what is the Hb content in Females
14.5 g/dL
what is the Hb content in males
15 g/dL
what is the Hb content at birth
25 g/dL
what is the Hb content after 3 months
20 g/dL
what is the Hb content in puberty
17 g/dL
what is the Hb content in adult
14 to 16 g/dL
What is Hb
Hemoglobin (Hb) is the iron containing coloring matter of (RBC). It is a chromoprotein forming 95% of dry weight of RBC and 30% to 34% of wet weight.
Function of hemoglobin is to carry the respiratory gases,
oxygen and carbon dioxide. It also acts as a buffer.
Molecular weight of hemoglobin is 68,000.
Comment on Hb synthesis
-Erythroblasts in the bone marrow undergo mitosis and begin making Hb, first by synthesizing haem and the polypeptide chains of globin separately and then by combining them to form Hb
-Synthesis of haem begins in the mitochondria with the condensation of succinyl coenzyme-A and glycine to form δ-amino lavulinic acid. This step is controlled by the enzyme ALA-synthase which requires pyridoxine (Vit B6)`s co-factor and is inhibited by haem.
-Protoporphyrin IX is formed after several reactions and the enzyme ferrochelatase catalyses the insertion of ferrous iron into the protoporphyrin ring to form heam.
-Each haem molecule combines with a polypeptide chain, a globin synthesized by ribosomes, forming a subunit of Hb called a Hb chain (MW – 16,000)
-4 of these bind together loosely to form the whole haemoglobin molecule.
what are the functions of Hb
-Transport of Oxygen
-Transport of carbon dioxide
- Buffering agent
Comment on Hb function of oxygen transport
When oxygen binds with Hb, a physical process called oxygenation occurs, resulting in the formation of oxyhemoglobin. The iron remains in ferrous state in this compound. Oxyhemoglobin is an unstable compound and the combination is reversible, i.e. when more oxygen is available, it combines with Hb and whenever oxygen is required, Hb can release oxygen
readily .
When oxygen is released from oxyhemoglobin, it is
called reduced Hb or ferrohemoglobin.
Hb function of Co2 Transport ?
When carbon dioxide binds with Hb, carbhemoglobin is formed. It is also an unstable compound and the combination is reversible, i.e. the carbon dioxide can be released from this compound. The affinity of Hb for carbon dioxide is 20 times more than that for oxygen.
How is Hb a buffer
Hemoglobin acts as a buffer and plays an important role in acidbase balance
what are the 2 types of normal Hb
> Adult haemoglobin – HbA, (2α and 2β) and
Fetal haemoglobin – HbF (2α and 2γ- chains).
WHAT is abnormal Hb
Abnormal types of hemoglobin or hemoglobin variants are the pathologic mutant forms of hemoglobin. These variants are produced because of structural changes in the polypeptide chains caused by mutation in the genes of the globin chains
what are the types of abnormal Hb
-Hemoglobinopathies
-Hemoglobin in thalassemia and related disorders.
What are the Hemoglobinopathies
Hemoglobinopathy is a genetic disorder caused by abnormal polypeptide chains of hemoglobin. Some of the hemoglobinopathies are:
-HbS
-HbE
-HbM
-HbC
Comment on HbC
The β-chains are abnormal. It is found in people with hemoglobin C disease, which is characterized by mild hemolytic anemia and splenomegaly
Comment on HbC
The β-chains are abnormal. It is found in people with hemoglobin C disease, which is characterized by mild hemolytic anemia and splenomegaly
comment on HbM
It is the abnormal Hb present in the form of methemoglobin. It occurs due to mutation of genes of both in α and β chains, resulting in abnormal replacement of amino acids. It is present in babies affected by HbM disease or blue baby syndrome. It is an inherited disease, characterized by methemoglobinemia.
comment on HbE
Here also the β-chains are abnormal. It is present in people with HbE disease which is also characterized by mild hemolytic anemia and splenomegaly.
comment on HbS
the most common hemoglobinopathy being sickle cell anaemia. Hb molecule has an abnormal β chain, in which valine replaces glutamine in the 6th position of the β-chain of globin.
what is thalassemia
This group of disorders is characterized by failure to synthesize normal quantities of Hb. The disorder is termed α or β – thalassaemia, depending upon which chain is synthesized in reduced quantities.
Some of the abnormal hemoglobins found in thalassemia are hemoglobin G, H, I, Bart’s, Kenya, Lepore and constant spring.
comment on the destruction of RBC
-RBCs are destroyed in the reticuloendothelial system (spleen) and the Hb will be released in plasma.
-Hb is degraded by the reticuloendothelial cells and split into globin and iron and porphyrin.
-Globin is utilized for the resynthesis of Hb.
-Heme is degraded into iron and porphyrin.
-Iron is stored in the body as ferritin and hemosiderin, which are reutilized for the synthesis of new Hb.
-Porphyrin is converted into a green pigment called biliverdin
-Most of the biliverdin is converted into yellow pigments called bilirubin which are removed by the liver as bile.
-A yellow tint of the skin and eyes caused by the excess of bilirubin is called jaundice an inflamed liver can also jaundice.
what is anemia
Anaemia is deficiency of Hb in the blood which is caused by too few RBC or decrease Hb concentration in the RBC, or PCV. Anaemia will occur if there is reduction in RBC count, Hb content and packet cell volume.
what are the general causes of anemia
- Decreased production of RBC
- Increased destruction of RBC
- Excess loss of blood from the body
what are the groups for classifying anemia
(1) Morphological classification base of the size shape of the RBC.
(2) Etiological classification (causes of the anaemia)
what are the groups for classifying anemia
(1) Morphological classification base of the size shape of the RBC.
(2) Etiological classification (causes of the anaemia)
WHAT ARE THE MORPHOLOGICAL CLASSIFICATIONS OF ANEMIA
-Normocytic normochromic
-Microcytic hypochromic
-Macrocytic hypochromic
-Macrocytic normochromic
how do you know the size of an RBC
mean corpuscular volume (MCV).
how do you find the Hb content or color of an RBC
Color is determined by mean corpuscular hemoglobin concentration (MCHC)
what is normocytic normochromic anemia
Size (MCV) and color (MCHC) of RBCs are normal. But the number of RBC is less
what is microcytic hypochromic anemia
RBCs are smaller in size with less Hb/ color (MCHC)
what is macrocytic hypochromic anemia
RBCs are larger in size with normal Hb levels/color. RBC count is less.
what is macrocytic normochromic anemia
RBCs are larger in size. MCHC is less, so the cells are
pale (less colored).
what are the etiological classifications of anemia
- Hemorrhagic anemia
- Hemolytic anemia
- Nutrition deficiency anemia
- Aplastic anemia
- Anemia of chronic diseases.
comment on hemorraghic anemia
Hemorrhage refers to excessive loss of blood. Hemorrhage can occur in condition like accident, ulcer, excessive uterine bleeding, purpura and haemophilia.
It has 2 types:
-chronic
-acute
what is chronic hemorrhage guy
It refers to loss of blood by internal or external bleeding,
over a long period of time. It occurs in conditions like
peptic ulcer, purpura, hemophilia and menorrhagia. Due to continuous loss of blood, lot of iron is lost from the body causing iron deficiency. This affects the synthesis of hemoglobin resulting in less hemoglobin content in the cells. The cells also become small. Hence, the RBCs are microcytic and hypochromic
what is acute hemorrhage
Acute hemorrhage refers to sudden loss of a large quantity of blood as in the case of accident. Within about 24 hours after the hemorrhage, the plasma portion of blood
is replaced. However, the replacement of RBCs does not occur quickly and it takes at least 4 to 6 weeks. So with less number of RBCs, hemodilution occurs. However, morphologically the RBCs are normocytic and normochromic
what is hemolytic anemia
Hemolysis means destruction of RBCs. Anemia due to excessive hemolysis which is not compensated by increased RBC production is called hemolytic anemia. It is classified into two types:
A. Extrinsic hemolytic anemia.
B. Intrinsic hemolytic anemia.
what is extrinsic hemolytic anemia
It is the type of anemia caused by destruction of RBCs by external factors. Healthy RBCs are hemolized by factors outside the blood cells such as antibodies, chemicals and drugs. Extrinsic hemolytic anemia is also called autoimmune
hemolytic anemia. Common causes of external hemolytic anemia:
i. Liver failure
ii. Renal disorder
iii. Hypersplenism
iv. Burns
v. Infections like hepatitis, malaria and septicemia
vi. Drugs such as penicillin, antimalarial drugs and sulfur drugs
vii. Poisoning by chemical substances like lead, coal and tar
viii. Presence of isoagglutinin’s like antiRh
ix. Autoimmune diseases such as rheumatoid arthritis and ulcerative colitis.
what is extrinsic hemolytic anemia
It is the type of anemia caused by destruction of RBCs by external factors. Healthy RBCs are hemolized by factors outside the blood cells such as antibodies, chemicals and drugs. Extrinsic hemolytic anemia is also called autoimmune
hemolytic anemia. Common causes of external hemolytic anemia:
i. Liver failure
ii. Renal disorder
iii. Hypersplenism
iv. Burns
v. Infections like hepatitis, malaria and septicemia
vi. Drugs such as penicillin, antimalarial drugs and sulfur drugs
vii. Poisoning by chemical substances like lead, coal and tar
viii. Presence of isoagglutinin’s like antiRh
ix. Autoimmune diseases such as rheumatoid arthritis and ulcerative colitis.
causes of extrinsic hemolytic anemia
i. Liver failure
ii. Renal disorder
iii. Hypersplenism
iv. Burns
v. Infections like hepatitis, malaria and septicemia
vi. Drugs such as penicillin, antimalarial drugs and sulfur drugs
vii. Poisoning by chemical substances like lead, coal and tar
viii. Presence of isoagglutinin’s like antiRh
ix. Autoimmune diseases such as rheumatoid arthritis and ulcerative colitis.
what is intrinsic hemolytic anemia
It is the type of anemia caused by destruction of RBCs because of the defective RBCs. There is production of unhealthy RBCs, which are short lived and are destroyed soon. Intrinsic hemolytic anemia is often inherited.Because of the abnormal shape in sickle cell anemia and thalassemia, the RBCs become more fragile and susceptible for hemolysis.
it includes:
sickle cell anemia and
thalassemia (alpha and beta)
comment on sickle cell anemia
Sickle cell anemia is due to the abnormal hemoglobin called hemoglobin S (sickle cell hemoglobin). In this, αchains are normal and βchains are abnormal. The molecules of hemoglobin S polymerize into long chains and precipitate inside the cells. Because of this, the RBCs attain sickle (crescent) shape and become more fragile leading to hemolysis. Sickle cell anemia occurs when a person inherits two abnormal genes (one from each parent).
In children, hemolyzed sickle cells aggregate and block the blood vessels, leading to infarction (stoppage of blood supply). The infarction is common in small bones. The infarcted small bones in hand and foot results in varying length in the digits. This condition is known as hand and foot syndrome. Jaundice also occurs in these children.
what is thalassemia
In normal Hb, number of α and β polypeptide
chains is equal. In thalassemia, the production of these
chains become imbalanced because of defective synthesis of globin genes. This causes the precipitation of the polypeptide chains in the immature RBCs, leading to disturbance in erythropoiesis. The precipitation also occurs in mature red cells, resulting in hemolysis.
Thalassemia is of 2 types:
i. α-thalassemia.
ii. β-thalassemia.
what is thalassemia
In normal Hb, number of α and β polypeptide
chains is equal. In thalassemia, the production of these
chains become imbalanced because of defective synthesis of globin genes. This causes the precipitation of the polypeptide chains in the immature RBCs, leading to disturbance in erythropoiesis. The precipitation also occurs in mature red cells, resulting in hemolysis.
Thalassemia is of 2 types:
i. α-thalassemia.
ii. β-thalassemia.
what is α thalassemia
α-thalassemia occurs in fetal life or infancy. In this αchains are less, absent or abnormal. In adults, βchains are in excess and in children, γchains are in excess. This leads to defective erythropoiesis and hemolysis. The infants may be stillborn or may die immediately after birth.
what is β thalassemia
In βthalassemia, βchains are less in number, absent or abnormal with an excess of αchains. The αchains precipitate causing defective erythropoiesis and hemolysis
what is nutrition deficiency anemia
Anemia that occurs due to deficiency of a nutritive substance necessary for erythropoiesis is called nutrition deficiency anemia. The substances which are necessary for erythropoiesis are iron, proteins and vitamins like C, B12 and folic acid. The types of nutrition deficiency anemia are:
-Iron deficiency anemia
-Pernicious anemia
-protein deficiency anemia
-Megaloblastic anemia
comment on iron deficiency anemia
Iron deficiency anemia is the most common type of anemia. It develops due to inadequate availability of iron for Hb synthesis. RBCs are microcytic and hypochromic.
Causes of iron deficiency anemia:
i. Loss of blood
ii. Decreased intake of iron
iii. Poor absorption of iron from intestine
iv. Increased demand for iron in conditions like growth and pregnancy.
Symptoms: brittle nails, spoonshaped nails (koilonychias), brittle hair, atrophy of papilla in tongue and dysphagia (difficulty in swallowing).
comment on protein defiency anemia
Due to deficiency of proteins, the synthesis of hemoglobin
is reduced. The RBCs are macrocytic and hypochromic.
comment on pernicious anemia
Pernicious anemia is the anemia due to deficiency of vitamin B12. It is also called ADDISON’S ANEMIA. It is due to atrophy of the gastric mucosa because of autoimmune destruction of parietal cells.
The gastric atrophy results in decreased production of intrinsic factor and poor absorption of vitamin B12, which is the maturation factor for RBC.
RBCs are larger and immature with almost normal or slightly low hemoglobin level. Synthesis of hemoglobin is almost normal in this type of anemia. So, cells are macrocytic and normochromic or hypochromic.
Symptoms: lemon yellow color of skin (due to anemic paleness and mild jaundice) and red sore tongue. Neurological disorders such as paresthesia (abnormal sensations like numbness, tingling, burning, etc.), progressive weakness and ataxia (muscular incoordination)
comment on megaloblastic anemia
Megaloblastic anemia is due to the deficiency of another
maturation factor called folic acid. Here, the RBCs are not matured. The DNA synthesis is also defective, so the nucleus remains immature. The RBCs are megaloblastic and hypochromic.
Symptoms pernicious anemia appear in megaloblastic
anemia also. However, neurological disorders may not
develop
comment on aplastic anemia
Aplastic anemia is due to the disorder of red bone marrow. Red bone marrow is reduced and replaced by fatty tissues. Bone marrow disorder occurs in the following conditions:
i. Repeated exposure to Xray or gamma ray radiation.
ii. Presence of bacterial toxins, quinine, gold salts, benzene, radium, etc.
iii. Tuberculosis.
iv. Viral infections like hepatitis and HIV infections.
In aplastic anemia, the RBCs are normocytic and normochromic.
causes of aplastic anemia
i. Repeated exposure to Xray or gamma ray radiation.
ii. Presence of bacterial toxins, quinine, gold salts, benzene, radium, etc.
iii. Tuberculosis.
iv. Viral infections like hepatitis and HIV infections.
comment on anemia of chronic diseases
It is characterized by short lifespan of RBCs, caused by disturbance in iron metabolism or resistance to erythropoietin action. Anemia develops after few months of sustained disease. RBCs are normocytic and normochromic. \
Common causes anemia of chronic diseases:
i. Noninfectious inflammatory diseases such as rheumatoid arthritis (chronic inflammatory autoimmune disorder affecting joints).
ii. Chronic infections like tuberculosis (infection caused by Mycobacterium tuberculosis) and abscess (collection of pus in the infected tissue) in lungs.
iii. Chronic renal failure, in which the erythropoietin secretion decreases (since erythropoietin is necessary for the stimulation of bone marrow to produce RBCs, its deficiency causes anemia).
iv. Neoplastic disorders (abnormal and disorganized growth in tissue or organ) such as Hodgkin’s disease (malignancy involving lymphocytes) and cancer of lung and breast.
RBCs are generally normocytic and normochromic in this type of anemia. However, in progressive disease associated with iron deficiency the cells become microcytic and hypochromic
what are the causes of anemia of chronic disease
i. Noninfectious inflammatory diseases such as rheumatoid arthritis (chronic inflammatory autoimmune disorder affecting joints).
ii. Chronic infections like tuberculosis (infection caused by Mycobacterium tuberculosis) and abscess (collection of pus in the infected tissue) in lungs.
iii. Chronic renal failure, in which the erythropoietin secretion decreases (since erythropoietin is necessary for the stimulation of bone marrow to produce RBCs, its deficiency causes anemia).
iv. Neoplastic disorders (abnormal and disorganized growth in tissue or organ) such as Hodgkin’s disease (malignancy involving lymphocytes) and cancer of lung and breast.
what are the symptoms of anemia
-Skin: Brittle nails, color of the skin and mucous membrane becomes pale, paleness is more constant and prominent in buccal, pharyngeal mucous membrane, conjunctivae, lips, ear
lobes, palm and nail bed.
-CVS: tachycardia, blood vessel is dilated and cardiac murmurs are produced, velocity of blood flow is increased.
-Respiration: There is an increase in rate and force of respiration, it leads to breathlessness and dyspnea (difficulty in breathing), Oxygenhemoglobin dissociation curve is shifted to right.
-Digestive system: Anorexia, nausea, vomiting, abdominal discomfort and constipation are common. In pernicious anemia, there is atrophy of papillae in tongue. In aplastic anemia, necrotic lesions appear in mouth and pharynx.
-Metabolism: Basal metabolic rate increases in severe anemia
-Kidney: Renal function is disturbed. Albuminuria is common.
-Reproduction: In females, the menstrual cycle is disturbed. There may be menorrhagia, oligomenorrhea or amenorrhea
-Neuromuscular junction: increased sensitivity to cold, headache, lack of concentration, restlessness, irritability, drowsiness, dizziness or vertigo (especially while standing) and fainting. Muscles become weak and the patient feels a lack of energy and fatigued quite often and quite easily
comparison between WBC and RBC
- Larger in size.
- Irregular in shape.
- Nucleated.
- Many types.
- Granules are present in some type of WBCs.
- Lifespan is shorter.
what is the normal WBC count
4,000 to 11,000/cu mm
what is the maximum diameter of WBC
18 µ
what is the lifespan of WBC
½ to 15 days
what are the 2 groups of WBC classification
- Granulocytes which have granules.
- Agranulocytes which do not have granules
what are the granulocytes
i. Neutrophils with granules taking both acidic and basic stains.
ii. Eosinophils with granules taking acidic stain.
iii. Basophils with granules taking basic stain
what are the agranulocytes
i. Monocytes.
ii. Lymphocytes
comment on neutrophils
Along with monocytes, the neutrophils provide the first line of defense against the invading microorganisms. They are:
-10 to 12µ in diameter.
-They have 2 – 5 lobes and fine granules in the cytoplasm. -They have a lifespan of 2-5days.
-They have a % composition of 40 to 60
-They have a volume of 3,000 to 6,000 cu.mm
The granules contain NADPH oxidase catalase, myeloperoxidase plus antimicrobial proteins called defensins (α and β). When stained with Leishman stain, the granules appear violet in colour.
comment on eosinophils
Eosinophils have coarse (larger) granules in the cytoplasm, which stain pink or red with eosin. Nucleus is bilobed and spectacle-shaped. Eosinophils play an important role in the defense mechanism of the body against the parasites. During
parasitic infections, there is a production of a large number of eosinophils which move towards the tissues affected by parasites. Eosinophils are responsible for detoxification, disintegration and removal of foreign proteins.
-Diameter of the cell varies between 10 and 14 µ.
-lifespan is 7 to 12 days
-% composition is 2 to 4
-volume is 150 to 450 Cu.mm
comment on basophils
Basophils also have coarse granules in the cytoplasm.
The granules stain purple blue with methylene blue.
Nucleus is bilobed.
-Diameter of the cell is 8 to 10 µ.
-lifespan is 12 to 15 days
-% composition is 0 to 1%
-Volume is 0 to 100cu.mm
Basophils play an important role in healing processes.
So their number increases during healing process. Basophils also play an important role in allergy or acute hypersensitivity reactions (allergy). This is because of the presence of receptors for IgE in basophil membrane.
comment on monocytes
Monocytes are the largest leukocytes with diameter of 14 to 18 µ. The cytoplasm is clear without granules. Nucleus is round, oval and horseshoe shaped, bean shaped or kidney shaped. Nucleus is placed either in the center of the cell or pushed to one side and a large amount of cytoplasm is seen.
-diameter is 14 to 18
-lifespan is 2 to 5days
-% composition is 2 to 6
- volume is 200 to 600cu.mm
Monocytes are the largest cells among the leukocytes.
Like neutrophils, monocytes also are motile and
phagocytic in nature. These cells wander freely through
all tissues of the body.
Along with neutrophils, these leukocytes provide the first line of defense.
Monocytes secrete:
1. Interleukin-1 (IL-1).
2. Colony stimulating factor (M-CSF).
3. Platelet-activating factor (PAF).
what chemicals does a monocyte secrete
- Interleukin-1 (IL-1).
- Colony stimulating factor (M-CSF).
- Platelet-activating factor (PAF).
comment on leukocyte
Like monocytes, the lymphocytes also do not have
granules in the cytoplasm. Nucleus is oval, bean-shaped
or kidney-shaped. Nucleus occupies the whole of the
cytoplasm. A rim of cytoplasm may or may not be seen
-Diameter: 7 to 12
-Lifespan: ½ to 1
-% comp. 20 to 30
- Volume 1,500 to 2,700 Cu.mm
Lymphocytes play an important role in immunity. Functionally, the lymphocytes are classified into two categories, namely T lymphocytes and B lymphocytes.
T lymphocytes are responsible for the development of cellular immunity and B lymphocytes are responsible for the development of humoral immunity
what factors aid phagocytosis
-Surface of particle is rough.
-Lacks protective protein coat.
-Binding of antibodies to antigen (opsonization).
What is leucopoiesis
Leucopoiesis is the process by which white blood cells (leukocytes) are produced in the body. It involves the differentiation of hematopoietic stem cells into various types of white blood cells, including granulocytes, monocytes, and lymphocytes. This process is regulated by various cytokines and growth factors, which stimulate the proliferation and differentiation of precursor cells into mature white blood cells
draw a chart to show leucopoiesis
check your fucking book
draw a chart to show erythropoiesis
just check the book
what are the sites of WBC production
lymph glands,
spleen,
thymus,
tonsils and various packed lymphoid tissues elsewhere in the body such as
-the bone marrow and
-in payer’s patches underneath the epithelium in the gut walls
regulation of leucopoiesis?
Many growth factors are involved in the maturation process of leucocytes.
These are interleukin – 1 (IL – 1), IL – 3, 5, 6, 11
granulocyte-macrophage colony–stimulating factor (GM – CSF) granulocyte CSF (G – CSF) and
monocyte CSF (M – CSF).
what is leukocytosis
Leukocytosis is the increase in total leukocyte (WBC) count. It occurs in conditions such as:
1. Infections
2. Allergy
3. Common cold
4. Tuberculosis
5. Glandular fever.
wetin be leukemia
Leukemia is the condition which is characterized by abnormal and uncontrolled increase in leukocyte count more than 1,000,000/cu mm. It is also called blood cancer.
what is leukopenia
Leukopenia is the decrease in the total WBC count. It occurs in the following pathological conditions:
1. Anaphylactic shock
2. Cirrhosis of liver
3. Disorders of spleen
4. Pernicious anemia
5. Typhoid and paratyphoid
6. Viral infections.
what are the physiological variations of WBC count
- Age: WBC count is about 20,000 per cu.mm in INFANTS and about 10,000 to 15,000 per cu.mm of blood in CHILDREN. In ADULTS, it ranges between 4,000-11,000 per cu.mm of blood.
- Sex: Slightly more in males than in females.
- Diurnal variation: Minimum in early morning and
maximum in the afternoon.
What is immunity
Immunity is defined as the capacity of the body to resist
pathogenic agents. It is the ability of body to resist the
entry of different types of foreign bodies like bacteria,
virus, toxic substances
What are the 2 types of immunity
I. Innate immunity.
II. Acquired immunity.
What is innate immunity
Innate immunity is the inborn capacity of the body to
resist pathogens. By chance, if the organisms enter
the body, innate immunity eliminates them before the
development of any disease. It is otherwise called the
natural or non-specific immunity
What are the mechanisms of innate immunity
GIT:Enzymes in digestive juices and the acid in stomach destroy the toxic substances or
organisms entering digestive tract through food. Lysozyme present in saliva destroys bacteria
Respo: Defensins and cathelicidins in epithelial cells of air passage are antimicrobial peptides. Neutrophils, lymphocytes, macrophages and natural killer cells present in lungs act
against bacteria and virus
Urogenital: Acidity in urine and vaginal fluid destroy the bacteria
Skin: The keratinized stratum corneum of epidermis protects the skin against toxic chemicals.
The β-defensins in skin are antimicrobial peptides.
Lysozyme secreted in skin destroys bacteria
Phagocytic cells:
Neutrophils, monocytes and macrophages ingest and destroy the microorganisms and
foreign bodies by phagocytosis
Interferons
: Inhibit multiplication of viruses, parasites and cancer cells
Complement proteins:
Accelerate the destruction of microorganisms
What is acquired immunity
Acquired immunity is the resistance developed in the
body against any specific foreign body like bacteria,
viruses, toxins, vaccines or transplanted tissues
What are the types of acquired immunity
Cellular immunity
Humoral immunity
What are the 2 types of acquired immunity
T lymphocytes or T cells, which are responsible for
the development of cellular immunity
B lymphocytes or B cells, which are responsible for
humoral immunity
What are the types of T lymphocytes
- Helper T cells or inducer T cells. These cells are
also called CD4 cells because of the presence of
molecules called CD4 on their surface. - Cytotoxic T cells or killer T cells. These cells are
also called CD8 cells because of the presence of
molecules called CD8 on their surface. - Suppressor T cells.
- Memory T cells.
What are the T lymphocytes
T lymphocytes are processed in thymus. The processing
occurs mostly during the period between just before birth
and few months after birth.
Thymus secretes a hormone called thymosin, which
plays an important role in immunity. It accelerates the
proliferation and activation of lymphocytes in thymus. It
also increases the activity of lymphocytes in lymphoid
tissues
Where are T lymphocytes stored
After the transformation, all the types of T lymphocytes
leave the thymus and are stored in lymphoid tissues of
lymph nodes, spleen, bone marrow and GI tract.
What are the types of B cells
- Plasma cells.
- Memory cells.
Storage of B cells ?
After transformation, the B lymphocytes are stored in the
lymphoid tissues of lymph nodes, spleen, bone marrow
and the GI tract.
What is humoral immunity
Humoral immunity is defined as the immunity mediated
by antibodies, which are secreted by B lymphocytes.
B lymphocytes secrete the antibodies into the blood
and lymph. The blood and lymph are the body fluids
(humours or humors in Latin). Since the B lymphocytes
provide immunity through humors, this type of immunity
is called humoral immunity or B cell immunity.
Antibodies are the gamma globulins produced by B
lymphocytes. These antibodies fight against the invading
organisms. The humoral immunity is the major defense
mechanism against the bacterial infection
What is cell mediated immunity
Cell-mediated immunity is defined as the immunity
developed by cell-mediated response. It is also called
cellular immunity or T cell immunity. It involves several
types of cells such as T lymphocytes, macrophages and
natural killer cells and hence the name cell mediated
immunity. Cell-mediated immunity does not involve
antibodies.
Cellular immunity is the major defense mechanism
against infections by viruses, fungi and few bacteria like
tubercle bacillus. It is also responsible for delayed allergic
reactions and the rejection of transplanted tissues.
Cell-mediated immunity is offered by T lymphocytes
and it starts developing when T cells come in contact
with the antigens. Usually, the invading microbial or
non-microbial organisms carry the antigenic materials.
These antigenic materials are released from invading
organisms and are presented to the helper T cells by
antigen-presenting cells.
Draw a chart on immunity
Check your book
What are natural killer cells
The NK cell is a large granular cell with indented nucleus. It is considered as the third type of lymphocyte and it is often called the non – T, non – B cell. NK cell kills the invading organisms or the cells of the body without prior sensitization. It is not a phagocytic cell but it has granules that contains hydrolytic enzymes which play an important role in the lysis of cells.
What is the complement system
Complement is a collective term that describes a system of about 20 proteins many of which are precursors. The main actors in the system are 11 proteins designated C1 through C9. These are present in the plasma protein in the blood. The enzymes precursors are normally inactive, but they can be activated mainly by antigen – antibody reaction.
What are the pathways formed by complement
a. Classical pathway
b. Lectin pathway
c. Alternate pathway.
The classical complement pathway?
In this the C1
binds with the antibodies and triggers a
series of events in which other enzymes are activated
in sequence. These enzymes or the byproducts formed
during these events produce the following activities:
i. Opsonization: Activation of neutrophils and macrophages to engulf the bacteria, which are bound
with a protein in the plasma called opsonin.
ii. Lysis: Destruction of bacteria by rupturing the
cell membrane.
iii. Chemotaxis: Attraction of leukocytes to the site
of antigen-antibody reaction.
iv. Agglutination: Clumping of foreign bodies like
RBCs or bacteria.
v. Neutralization: Covering the toxic sites of
antigenic products.
vi. Activation of mast cells and basophils, which
liberate histamine: Histamine dilates the blood
vessels and increases capillary permeability.
So, plasma proteins from blood enter the tissues
and inactivate the antigenic products
Outline the steps in the classical complement pathway
i. Opsonization: Activation of neutrophils and macrophages to engulf the bacteria, which are bound
with a protein in the plasma called opsonin.
ii. Lysis: Destruction of bacteria by rupturing the
cell membrane.
iii. Chemotaxis: Attraction of leukocytes to the site
of antigen-antibody reaction.
iv. Agglutination: Clumping of foreign bodies like
RBCs or bacteria.
v. Neutralization: Covering the toxic sites of
antigenic products.
vi. Activation of mast cells and basophils, which
liberate histamine: Histamine dilates the blood
vessels and increases capillary permeability.
So, plasma proteins from blood enter the tissues
and inactivate the antigenic products
Lectin pathway of complement proteins?
Lectin pathway occurs when mannose-binding lectin
(MBL), which is a serum protein binds with mannose or
fructose group on wall of bacteria, fungi or virus
Comment on the alternate pathway of complement action
It is due to a protein in
circulation called factor I. It binds with polysaccharides
present in the cell membrane of the invading organisms.
This binding activates C3 and C5, which ultimately attack
the antigenic products of invading organism.
What is specificity of B cells
Each B lymphocyte is designed to be activated only
by one type of antigen. It is also capable of producing
antibodies against that antigen only. This property of
B lymphocyte is called specificity. In lymphoid tissues,
the lymphocytes, which produce a specific antibody, are
together called the clone of lymphocytes.
What are platelets
Platelets or thrombocytes are the formed elements of
blood. Platelets are small colorless, non-nucleated and
moderately refractive bodies.
Diameter : 2.5 µ (2 to 4 µ)
Volume : 7.5 cu µ (7 to 8 cu µ).
Lifespan: 8-11 days
Count: 200,000 and 400,000/cu mm
What are the functions of glycoproteins in platelet cell membrane
Glycoproteins prevent the adherence of platelets to normal endothelium, but accelerate the adherence of platelets
to collagen and damaged endothelium in ruptured blood
vessels. Glycoproteins also form the receptors for:
👉adenosine diphosphate (ADP) and
👉thrombin.
What’s the function of phospholipids in cell membrane
Phospholipids accelerate the clotting reactions. The
phospholipids form the precursors of:
👉thromboxane A2
👉and other prostaglandin-related substances.
What are the proteins in the cytoplasm of the platelets
👉Contractile proteins: Actin, myosin,thrombosthenin
👉von willebrand factor
👉Platelet derived growth factor (PDGF)
👉Platelet activating factor (PAF)
👉fibrin stabilizing factor
👉Vitronectin
👉Thrombospondin
What are the functions of the contractile proteins in cell cytoplasm
i. Actin and myosin: Contractile proteins, which
are responsible for contraction of platelets.
ii. Thrombosthenin: Third contractile protein, which
is responsible for clot retraction
What is the function of von willebrand factor in the cytoplasm of the platelets
Responsible for adherence
of platelets and regulation of plasma level of factor
8.
What is the function of fibrin stabilizing factor in the cytoplasm of the platelets
Clotting factor 13
What is the function of Platelet derived growth factor in the cytoplasm of the platelets
Responsible
for repair of damaged blood vessels and wound
healing. It is a potent mytogen (chemical agent that
promotes mitosis) for smooth muscle fibers of blood
vessels.
Function of platelet activating factor in the cytoplasm of the platelets
Causes aggregation of platelets during the injury of blood vessels,
resulting in prevention of excess loss of blood.
Function of Vitronectin in the cytoplasm of the platelets
Promotes
adhesion of platelets and spreading of tissue cells in
culture
Function of Thrombospondin in the cytoplasm of the platelets
Inhibits angiogenesis (formation
of new blood vessels from pre-existing vessels).
What are the enzymes in the cytoplasm of the platelets
- Adensosine triphosphatase (ATPase)
- Enzymes necessary for synthesis of prostaglandins.
What are the hormonal substances in the cytoplasm of the platelets
- Adrenaline
- 5-hydroxytryptamine (5-HT; serotonin)
- Histamine.
What are the granules in the cytoplasm of the platelets
- Alpha granules
- Dense granules.
What do the alpha granules contain?
- Clotting factors – fibrinogen, V and XIII
- Platelet-derived growth factor
- Vascular endothelial growth factor (VEGF)
- Basic fibroblast growth factor (FGF)
- Endostatin
- Thrombospondin.
What do the dense granules contain
- Nucleotides
- Serotonin
- Phospholipid
- Calcium
- Lysosomes.
What are the physiological variations of platelets
- Age: Platelets are less in infants (1,50,000 to
2,00,000/cu mm) and reaches normal level at 3rd
month after birth. - Sex: There is no difference in the platelet count
between males and females. In females, it is reduced
during menstruation. - High altitude: Platelet count increases.
- After meals: After taking food, the platelet count
increases.
What are the properties of platelets
Adhesiveness
Aggregation
Agglutination
Comment on adhesiveness of a platelet
Adhesiveness is the property of sticking to a rough
surface. During injury of blood vessel, endothelium is
damaged and the subendothelial collagen is exposed.
While coming in contact with collagen, platelets are
activated and adhere to collagen. Adhesion of platelets
involves interaction between von Willebrand factor
secreted by damaged endothelium and a receptor protein
called glycoprotein Ib situated on the surface of platelet
membrane.
Other factors which accelerate adhesiveness
are
collagen,
thrombin,
ADP,
Thromboxane A2,
calcium
ions,
P-selectin and
vitronectin
What is aggregation
Aggregation is the grouping of platelets. Adhesion is
followed by activation of more number of platelets by
substances released from dense granules of platelets.
During activation, the platelets change their shape
with elongation of long filamentous pseudopodia which
are called processes or filopodia.
Filopodia help the platelets aggregate together.
Activation and aggregation of platelets is accelerated
by
ADP,
thromboxane A2 and
platelet-activating factor
What is agglutination of the platelets
Agglutination is the clumping together of platelets.
Aggregated platelets are agglutinated by the actions of
some platelet agglutinins and platelet-activating factor.
What are the functions of platelets
👉 Haemostatic role – platelet play a role in blood clotting by activating intrinsic prothrombin activator, secreting PF3 Ca+ and clotting factors (FXiii, thrombin and fibrinogen). Formation of platelet plug and vasoconstrictors. The actin, myosin and thrombosthenin in platelet causes clott retraction.
👉 Role in repair of ruptured blood vessel platelets produces PDGF which repairs the damaged endothelieum of the ruptured blood vessels
👉 Defense mechanism – by forming agglutination, the platelet can encircle the invading organism or foreign bodies and destroy them by phagocytosis.
What things activate platelets
- Collagen, which is exposed during damage of blood
vessels - von Willebrand factor
- Thromboxane A2
- Platelet-activating factor
- Thrombin
- ADP
- Calcium ions
- P-selectin: Cell adhesion molecule secreted from
endothelial cells - Convulxin: Purified protein from snake venom.
What are the inhibitors of platelets
- Nitric oxide
- Clotting factors: 2, 9, 10, 11 and 12
- Prostacyclin
- Nucleotidases which breakdown the ADP.
Comment on the development of platelets
Platelets are formed from bone marrow. Pluripotent stem
cell gives rise to the colony forming unit-megakaryocyte
(CFU-M). This develops into megakaryocyte. Cytoplasm
of megakaryocyte form pseu do podium. A portion of
pseudopodium is detached to form platelet, which enters
the circulation.
Production of platelets is influenced by colony-stimulating factors and thrombopoietin. Colony-stimulating
factors are secreted by monocytes and T lymphocytes.
Thrombopoietin is a glycoprotein like erythropoietin. It is
secreted by liver and kidneys.
What are the platelet disorders
- Thrombocytopenia
- Thrombocytosis
- Thrombocythemia
- Glanzmann’s thrombasthenia
What is thrombocytopenia
Decrease in platelet count is called thrombocytopenia. It
leads to thrombocytopenic purpura
Thrombocytopenia occurs in the following
conditions:
i. Acute infections
ii. Acute leukemia
iii. Aplastic and pernicious anemia
iv. Chickenpox
v. Smallpox
vi. Splenomegaly
vii. Scarlet fever
viii. Typhoid
ix. Tuberculosis
x. Purpura
xi. Gaucher’s disease.
What are the causes of thrombocytopenia
i. Acute infections
ii. Acute leukemia
iii. Aplastic and pernicious anemia
iv. Chickenpox
v. Smallpox
vi. Splenomegaly
vii. Scarlet fever
viii. Typhoid
ix. Tuberculosis
x. Purpura
xi. Gaucher’s disease.
What is thrombocytosis
ncrease in platelet count is called thrombocytosis.
Thrombocytosis occurs in the following conditions:
i. Allergic conditions
ii. Asphyxia
iii. Hemorrhage
iv. Bone fractures
v. Surgical operations
vi. Splenectomy
vii. Rheumatic fever
viii. Trauma (wound or injury or damage caused by
external force).
Causes of thrombocytosis
i. Allergic conditions
ii. Asphyxia
iii. Hemorrhage
iv. Bone fractures
v. Surgical operations
vi. Splenectomy
vii. Rheumatic fever
viii. Trauma (wound or injury or damage caused by
external force).
What is thrombocythemia
Thrombocythemia is the condition with persistent and
abnormal increase in platelet count. Thrombocythemia
occurs in the following conditions:
i. Carcinoma
ii. Chronic leukemia
iii. Hodgkin’s disease.
What are the causes of thrombocythemia
i. Carcinoma
ii. Chronic leukemia
iii. Hodgkin’s disease.
What is glanzmanns thrombasthenia
Glanzmann’s thrombasthenia is an inherited hemorrhagic disorder, caused by structural or functional abnormality of platelets. It leads to thrombasthenic purpura. However, the platelet count is normal.
It is characterized by normal clotting time, normal or
prolonged bleeding time but defective clot retraction.
Draw a diagram to show the stages of hemostasis
Check the book guy
What is hemostasis
Haemostasis is a complex processes that lead to the arrest of bleeding of stoppage of bleeding.
What are the stages of hemostasis
- Vasoconstriction
- Platelet plug formation
- Coagulation of blood.
What is vasoconstriction in hemostasis
Immediately after the blood vessel is cut or severed, the blood vessel constricts to decrease the loss of blood. This vasoconstriction is as a result of reflex autonomic action, the real vasoconstriction occur after activated platelets secrete serotonin and thromboxane A2 which are vasoconstrictors.
What is platelet plug formation in hemostasis
When a blood vessel is cut, the result is adhesion of platelets to the exposed endothelial collagen, basement membrane and elastic fibres. Adhesion causes platelets to activate releasing substances like ADP, thromboxane A2 which attract more platelets to aggregate together and form platelet plug.
What is coagulation in hemostasis
Contact of blood with exposed collagen and elastic fibres initiates a complex series of reactions which result in the formation of fibrin. Blood clotting factors in the plasma are present in an inert proenzymes form. When a activated, are converted to an active form and inturn actives the other factors. This triggered enzyme system term a ‘cascade’ sequence of reaction.
Factor 1
fibrinogen
Factor 2
prothrombin
Factor 3
thromboplastin (Tissue factor)
Factor 4
Calcium
Factor 5
Labile factor (Proaccelerin or accelerator
globulin)
Factor 6
Dem never sabi
Factor 7
Stable factor
Factor 8
Antihemophilic factor (Antihemophilic
globulin)
Factor 9
Christmas factor
Factor 10
stuart-power factor
Factor 11
plasma thromboplastin artecedent
Factor 12
Hegman factor (contact factor)
Factor 13
Fibrin stabilizing factor
Draw a diagram to show blood clotting
Check the book
Draw a diagram with the intrinsic and extrinsic pathways
Check the book too
What is fibrinolysis.
fibrinolysis is the process of removing fibrin from circulation by degrading it enzymatically to fibrin degradation products (FDP). The purpose is to maintain potency in the vascular system controlling excess fibrin deposition on blood vessel wall. To do this plasminingen in the plasma in converted to plasmin.
What is blood coagulation
Coagulation or clotting is defined as the process in which
blood loses its fluidity and becomes a jelly-like mass few
minutes after it is shed out or collected in a container.
Explain enzymes cascade theory
Most of the clotting factors are proteins in the form of
enzymes. Normally, all the factors are present in the
form of inactive proenzyme. These proenzymes must
be activated into enzymes to enforce clot formation. It is
carried out by a series of proenzyme-enzyme conversion
reactions. First one of the series is converted into an
active enzyme that activates the second one, which
activates the third one; this continues till the final active
enzyme thrombin is formed.
Enzyme cascade theory explains how various
reactions, involved in the conversion of proenzymes
to active enzymes take place in the form of a cascade.
Cascade refers to a process that occurs through a series
of steps, each step initiating the next, until the final step
is reached.
What are the stages of blood clotting
- Formation of prothrombin activator
- Conversion of prothrombin into thrombin
- Conversion of fibrinogen into fibrin.
Outline the steps in intrinsic pathway
i. During the injury, the blood vessel is ruptured.
Endothelium is damaged and collagen beneath
the endothelium is exposed.
ii. When factor XII (Hageman factor) comes
in contact with collagen, it is converted into
activated factor XII in the presence of kallikrein
and high molecular weight (HMW) kinogen.
iii. The activated factor XII converts factor XI into
activated factor XI in the presence of HMW
kinogen.
iv. The activated factor XI activates factor IX in the
presence of factor IV (calcium).
v. Activated factor IX activates factor X in the
presence of factor VIII and calcium.
vi. When platelet comes in contact with collagen
of damaged blood vessel, it gets activated and
releases phospholipids.
vii. Now the activated factor X reacts with platelet
phos pholipid and factor V to form prothrombin
activa tor. This needs the presence of calcium
ions.
viii. Factor V is also activated by positive feedback
effect of thrombin (see below).
Why is it called the intrinsic pathway
the formation of prothrombin activator
is initiated by platelets, which are within the blood itself
Why is it called extrinsic pathways
the formation of prothrombin activator
is initiated by the tissue thromboplastin, which is formed
from the injured tissues.
Outline the steps of conversion of prothrombin to thrombin
i. Prothrombin activator that is formed in intrinsic
and extrinsic pathways converts prothrombin
into thrombin in the presence of calcium (factor
IV).
ii. Once formed thrombin initiates the formation of
more thrombin molecules. The initially formed
thrombin activates Factor V. Factor V in turn
accelerates formation of both extrinsic and
intrinsic prothrombin activator, which converts
prothrombin into thrombin. This effect of thrombin
is called positive feedback effect
Outline the steps of conversion of fibrinogen to fibrin
i. Thrombin converts inactive fibrinogen into
activated fibrinogen due to loss of 2 pairs of polypeptides from each fibrinogen molecule. The
activated fibrinogen is called fibrin monomer.
ii. Fibrin monomer polymerizes with other monomer
molecules and form loosely arranged strands of
fibrin.
iii. Later these loose strands are modified into dense
and tight fibrin threads by fibrin-stabilizing factor
(factor 13) in the presence of calcium ions. All the tight fibrin threads are aggregated
to form a meshwork of stable clot.
What are the investigations for bleeding disorders
Platelet count
Bleeding time
Clotting time
What is bleeding time
Bleeding time (BT) is the time interval from oozing of
blood after a cut or injury till arrest of bleeding. Usually,
it is determined by Duke method using blotting paper or
filter paper method. Its normal duration is 3 to 6 minutes.
It is prolonged in purpura.
What is clotting time
Clotting time (CT) is the time interval from oozing of
blood after a cut or injury till the formation of clot. It is
usually determined by capillary tube method. Its normal
duration is 3 to 8 minutes. It is prolonged in hemophilia.
What is prothrombin time
Prothrombin time (PT) is the time taken by blood to
clot after adding tissue thromboplastin to it
What are the 3 types of bleeding disorders
- Hemophilia.
- Purpura.
- von Willebrand disease.
What is hemophilia
Hemophilia is a group of sex-linked inherited blood
disorders, characterized by prolonged clotting time.
However, the bleeding time is normal. Usually, it affects
the males, with the females being the carriers.
Hemophilia occurs due to lack of formation of prothrombin
activator. That is why the coagulation time is prolonged.
The formation of prothrombin activator is affected due to
the deficiency of factor 8, 9 or 11.
Types of hemophilia are A,B,C
Symptoms of hemophilia:
i. Spontaneous bleeding.
ii. Prolonged bleeding due to cuts, tooth extraction
and surgery.
iii. Hemorrhage in gastrointestinal and urinary
tracts.
iv. Bleeding in joints followed by swelling and pain
v. Appearance of blood in urine.
Treatment: replacement of missing clotting factors
What is hemophilia A
Also called classical hemophilia, it is due to
the deficiency of factor 8. 85% of people with
hemophilia are affected by hemophilia A.
What is hemophilia B
Also called Christmas disease, it is due to
the deficiency of factor 9. 15% of people with
hemophilia are affected by hemophilia B.
What is hemophilia C
Also called factor 11 deficiency, it is due to the
deficiency of factor 11. It is a very rare bleeding
disorder.
What are the symptoms of hemophilia
i. Spontaneous bleeding.
ii. Prolonged bleeding due to cuts, tooth extraction
and surgery.
iii. Hemorrhage in gastrointestinal and urinary
tracts.
iv. Bleeding in joints followed by swelling and pain
v. Appearance of blood in urine.
What is purpura
Purpura is a disorder characterized by prolonged bleeding
time. However, the clotting time is normal. Characteristic
feature of this disease is spontaneous bleeding under
the skin from ruptured capillaries. It causes small tiny
hemorrhagic spots in many areas of the body. The
hemorrhagic spots under the skin are called purpuric
spots (purple colored patch like appearance). That is
why this disease is called purpura. Blood also sometimes
collects in large areas beneath the skin which are called
ecchymoses.
What is von willebrand diseas
von Willebrand disease is a bleeding disorder,
characterized by excess bleeding even with a mild injury.
It is due to deficiency of von Willebrand factor, which is
a protein secreted by endothelium of damaged blood
vessels and platelets. This protein is responsible for
adherence of platelets to the endothelium of blood vessels
during hemostasis after an injury. It is also responsible for
the survival and maintenance of factor VIII in plasma.
Deficiency of von Willebrand factor suppresses
platelet adhesion. It also causes deficiency of factor
8. This results in excess bleeding, which resembles
the bleeding that occurs during platelet dysfunction or
hemophilia.
What is thrombosis
Thrombosis or intravascular blood clotting refers to
coagulation of blood inside the blood vessels
Causes
Injury to the blood vessels
Roughened endothelium
Slow blood flow
Agglutination of RBC
Toxic thrombosis
Congenital absence of protein C
What is protein C
Protein C is a circulating anticoagulant, which inactivates
factors 5 and 8. Thrombosis occurs in the absence
of this protein. Congenital absence of protein C causes
thrombosis and death in infancy.
Importance of blood grouping
👉Medically blood grouping is important to avoid blood transfusion reaction by transfusing compatible blood.
👉Both ABO and Rhesus incompatibility can cause erythroblastosis fetalis. Blood grouping is necessary before marriage.
👉Blood grouping is helpful in medicolegal cases like maternal and paternal disputes.
👉Blood grouping is necessary for blood donation. The donor and the recipient blood group must be known.
👉Blood grouping is necessary for organ transplant since many tissues and organs also have these antigens.
What is a thrombus
During thrombosis, lumen of blood vessels is occluded.
The solid mass of platelets, red cells and/or clot, which
obstructs the blood vessel, is called thrombus. The
thrombus formed due to agglutination of RBC is called
agglutinative thrombus
What is embolism
Embolism is the process in which the thrombus or a
part of it is detached and carried in bloodstream and
occludes the small blood vessels, resulting in arrests of
blood flow to any organ or region of the body. Embolus
is the thrombus or part of it, which arrests the blood flow.
The obstruction of blood flow by embolism is common in
lungs (pulmonary embolism), brain (cerebral embolism)
or heart (coronary embolism).
What is ischeamia
Insufficient blood supply to an organ or area of the body
by the obstruction of blood vessels is called ischemia.
Ischemia results in tissue damage because of hypoxia
(lack of oxygen). Ischemia also causes discomfort, pain and tissue death. Death of body tissue is called
necrosis
What is infarction
Infarction means the tissue death due to loss of
blood supply. Loss of blood supply is usually caused
by occlusion of an artery by thrombus or embolus and
sometimes by atherosclerosis
What is necrosis
Necrosis is a general term that refers to tissue death
caused by loss of blood supply, injury, infection,
inflammation, physical agents or chemical substances.
