Physiology Flashcards
(287 cards)
1
Q
What is the lifespan for red blood cells?
A
120 days
2
Q
What is Erythropoiesis?
A
This is the production of red blood cells (erythrocytes)
3
Q
What is the nature of vitamin B-12?
A
Solely ANIMAL BASED
4
Q
What hormone is the process of Erythropoiesis regulated by?
A
Erythropoietin
5
Q
What are the primitive mother cells known as?
A
Pluripotent Stem Cells
They give rise to Myeloid cells and Lymphoid cells
6
Q
What is the order of growth for Erythropoiesis?
A
1.Stem Cell
2.Proerythroblast
3. Early erythroblast
4.Late Erythroblast
5.Normoblast
6.Reticulocyte
7.Erythrocytes
As cells mature the size decreases and their is a loss of nucleus. Nucleus function is replaced by certain enzymes in a fully mature cell. Haemoglobin is now present as cells mature.
7
Q
What are the necessary requirements for Erythropoiesis?
A
Iron man - IRON
Fought - FOLATE
Captain - COBALT SALT
America - ANDROGENS
Villans - VITAMIN B 12
” Iron man Fought Captain America Villans”
8
Q
Where is Erythropoietin produced?
A
90% - Kidney (Peritubular Interstitial cells)
10%- Liver
9
Q
What substances stimulate Erythropoietin production?
A
1.Oxygen Tension in tissues Kidneys
2. Hypoxia Inducible factors ( HIF -1 alpha and beta) under hypoxic conditions.
10
Q
What is the function of Erythrocytes?
A
Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs.
11
Q
What are the characteristics of Erythrocytes?
A
- Biconcave, Anucleate
- Contains Haemoglobin
- Contains Lipids, ATP, Carbonic Anhydrase
12
Q
How long does Erythropoiesis last for?
A
4-8 days
13
Q
What is the size of a regular RBC
A
7-8 microns
14
Q
What can Plasma Erythropoietin be used to diagnose?
A
Anaemia- They are high in anaemic persons
Renal disease or Polycythaemia Vera - They are low in persons with this disease.
15
Q
What is the function of the transcription factor GATA -2 ?
A
These are involved in initiating erythroid differentiation from Pluripotent cells.
” Gata is too(2) different”
16
Q
What is the function of transcription factors GATA- 1 and FOG-1 ?
A
They are important in enhancing the expression of erythroid-specific genes ex globin , haem biosynthetic and red cell membrane proteins.
17
Q
True or False?
The levels of Erythropoietin are high in persons with Polycythaemia vera and renal diseases?
A
FALSE!! Levels of Erythropoietin are LOW
18
Q
True or False?
The levels of Erythropoietin are High in persons with Anaemia or a person with a erythropoietin secreting tumour?
A
TRUE!!
19
Q
What is the dominant haemoglobin present in the blood after ages 3-6 months?
A
Haemoglobin A
20
Q
Characteristics of Haemoglobin A
A
Two alpha and two beta chains
21
Q
Where does Haem synthesis occurs?
A
In the mitochondria
22
Q
How long does Leucopoeisis lasts?
A
10-14 days
23
Q
What are the functions of Phagocytes?
A
The function of phagocytes and lymphocytes in protecting the body against infection is closely connected with two soluble protein systems of the body: immunoglobulins and complement.
24
Q
What is the lifecycle of granulocytes?
A
4-8 hrs in blood
4-5 days in the tissues
25
What is the lifespan of monocytes?
10- 20 hrs
26
What is Aplastic Anaemia?
Aplastic Anaemia is the condition where the body stops producing stem cells
27
Characteristics of Neutrophils
1. 5-6 lobed nucleus
2. Specific granules contain leukocyte alkaline phosphatase, myeloperoxidase, hydrolyses,lactoferrin,lysozyme,
3. Lifespan in blood is 6-10 hrs
4.First responders cells/ ,most frequent cells
5. Azurophilic granules (pink-blue in colour) contain proteinases, acid phosphatase, myeloperoxidase, and ~-glucuronidase.
28
What are the precursors of Neutrophils?
1.Myeoblast
2. Promyelocytes
3.Myelocytes
4.Metamyelocytes
5. Neutrophil
29
What are the different types of Neutrophils?
Non- Segmented - Immature neutrophils that can be seen in acute infections or inflammation. The bone marrow is sending out everything it has to fight an infection, even if the cells are not fully mature.
Segmented- mature or morphologically appropriate neutrophils with three to five nuclear lobes.
Hypersegmented- neutrophils usually have more than five lobes and are associated with vitamin
B12 or folate deficiencies.
30
What is the Ferrous state?
Fe2+
31
What is the Ferric state?
Fe 3+
32
By what pathway can Red blood cells generate ATP?
By Anaerobic Glycolytic pathway ( Embden-Meyerhof) pathway.
33
By what pathway can RBC's produce Glutathione?
By the Hexose monophosphate shunt (pentose phosphate) HMP shunt.
34
What is the overall process of the Embden-Meyerhof pathway ?
Converts glucose to lactate producing a net production of 2 ATP.
35
What is the main purpose of Gluthatione produced from the HMP shunt ?
It protects the red blood cells from oxidative stress - eliminating heamolysis.
36
Where does Haem synthesis occurs?
In the mitochondria.
37
Where do further Haem synthesis reactions take place?
In the cytoplasm.
38
Overview of Haem synthesis
1. Condensation of glycine and succinyl co-enzyme A under the KEY RATE- LIMITING enzyme δ‐aminolaevulinic acid (ALA) synthase .
2.Further reactions take place in the cytoplasm leading to the formation of protoporphyrin IX
3. The enzyme ferrochelatase catalyse the insertion of ferrous iron into protoporphyrin IX to form heme
4.This combines with globin chain to form haemoglobin molecule
39
What are the components of Adult Haemoglobin
2α chains
2β chains
40
What are the components of foetal haemoglobin?
2α chains
2 gamma chains
41
What are the clinical uses of erythropoietin?
Anaemia of chronic renal disease
Myelodysplastic syndrome
Anaemia associated with malignancy and chemotherapy
Anaemia of chronic diseases, e.g. rheumatoid arthritis
Anaemia of prematurity
Preoperative uses
42
What happens when the oxygen molecules are unloaded in a haemoglobin molecules?
When O2 is unloaded the β chains are pulled apart, permitting entry of the metabolite 2,3‐diphosphoglycerate (2,3‐DPG) resulting in a lower affinity of the molecule for O2.
43
True or false? When there is increased affinity to oxygen , the dissociation curve shifts to the right.
FALSE!! With increased affinity the curve shifts to the LEFT. With a decreased affinity the curve shifts to the RIGHT.
44
True or False? Faetal haemoglobin doesn't bind to 2,3 -DPG meaning they give up Oxygen less readily than normal.
TRUE!!
45
What is Methaemoglobinaemia ( Hb Ms)?
This is a clinical state in which circulating haemoglobin is present with iron in the oxidized (Fe3+) instead of the usual Fe2+ state.
( Fe2+ is the normal state haemoglobin is transferred in)
* It is present in intravascular haemolysis but NOT extravascular haemolysis
46
What disease has a symptom of cyanosis? ( blue-purple colouring of the skin?
Toxic Methemoglobinaemia. It occurs when a drug or other toxic substance oxidizes haemoglobin.
47
What is ptosis?
Drooping of the eyes
48
What is the normal haemoglobin value in men and women?
11.5- 15.5mmHg in Women
15.5- 17.5 mmHg in men
49
What is a next byproduct of Embden–Meyerhof pathway?
NADPH
50
What is the purpose of NADPH in this Embder-Meyherhof reaction?
It is needed by the enzyme methaemoglobin reductase to reduce functionally dead methaemoglobin containing ferric iron (produced by oxidation of approximately 3% of haemoglobin each day) to functionally active, reduced haemoglobin containing ferrous ions.
51
Which shunt produces 2,3 Diphosphoglyceric acid (2,3,DPG) which when bound to Hb, decreases its affinity for Oxygen leading to Oxygen delivery to tissues.
Luebering- Rapaport shunt.
52
What does a deficiency of pyruvate kinase cause?
Haemolysis of the cell
53
What process occurs in the HMP shunt?
Approximately 10% of glycolysis occurs by this oxidative pathway in which glucose‐6‐phosphate is converted to 6‐ phosphogluconate and so to ribulose‐5‐phosphate
54
Where is NADPH also generated?
The HMP shunt. It also produces Glutathione which maintains sulphhydril group (SH) groups intact in the cells and also haemoglobin.
55
What is as a result glucose‐6‐phosphate dehydrogenase (G6PD) deficiency?
Oxidative stress leading to episodic heamolysis of the cell.
56
How can oxidative stress arise?
Deficiency of G6PD and Pyruvate kinase
57
What are Heinz bodies?
These are erythrocyte structures composed of precipitated denatured haemoglobin.
58
What is the function of pyruvate kinase?
Pyruvate kinase catalyses the conversion of phosphoenol pyruvate to pyruvic acid, generating 2 molecules of ATP.
The ATP generated is used to maintain membrane integrity.
59
What are the clinical features of pyruvate kinase deficiency?
1. Chronic, non- spherocytic haemolytic anaemia
2.Splenomegaly and gall stones
60
What are gall stones comprised of?
They are comprised of calcium salts of unconjugated bilirubin from the chronic haemolysis.
61
True of false ?
RBCs cannot compensate for enzyme imperfections and cannot synthesize new enzymes to replace those that become exhausted during the cell's lifetime.
TRUE!!
62
What are the enzymes involved in glycolysis?
P PFKM – phosphofructokinase (PFK)
P GK1 – phosphoglycerate kinase (PGK
P - PKLR – pyruvate kinase (PK)
H - HK1 – hexoskinase isoform (HK)
G - GPI – glucose-6-phosphate isomerase (GPI)
"triple P , HG"
63
What are the enzymes involved in Glutathione metabolism?
G-G6PD – glucose-6-phosphate dehydrogenase
G-GSR- Glutathione reductase
G-GSS- Glutathione synthase
'Triple G'
64
What are the enzymes for Purine metabolism?
P - NT5C3A - pyrimidine 5 nucleotidase
A - ADA - Adenosine deaminase
65
What colour tube has an anticoagulant agent (EDTA) and can be used to identify blood count?
Purple top
66
What agent does a blue top use and what is tested for?
Trisodium citrate and is used for coagulation
67
What colour tube is used for molecular studies, cytogenics and lymphocyte count?
Green tube
68
What stain is used when testing the morphology of blood?
Wright or May- Grunwald -Giemsa stain
69
How long does it take a reticulocyte to mature
1 day
70
Where is Iron mainly absorbed?
Duodenum
71
What is the daily absorption of iron?
1 mg
72
What is the daily loss of iron for males?
1 mg
73
What are the factors favouring iron absorption?
1. Haem iron
2.Ferrous form (Fe2+)
3. Acids (Hcl, Vit C)
4. Solubilizing agents ( ex sugars, amino acids)
5.Reduced serum hepcidin
6.Ineffective erythropoiesis
7.Pregnancy
8.Hereditary haemochromatosis
74
What are factors reducing iron absorption?
1.Inorganic iron
2. Ferric form
3. Alkalis- antacids, pancreatic secretions
4. Precipitating agents
5.Increased serum hepcidin
6. Decreased erythropoiesis
7.Inflammation
8. Pytates(wheat, cereal), oxalates(tomato, spinach), carbonates, tannates (tea)
75
Where is iron normally stored?
Hepatocytes in the liver
76
What is the differences between inorganic iron and heam iron?
Inorganic iron - This is the iron coming from fruits and vegetables
Haem iron - This is the iron coming from animals ,and meats.
77
What is the daily loss of iron for females?
1.5 mg
78
What is a next name for Haemochromatosis?
Bronze diabetes
79
Where can Hemsosiderin be found?
In the macrophages
80
What is the soluble form of Iron?
Ferritin
81
True or False? Hemosiderin is an insoluble form of iron
TRUE!!
82
What is the name of the protein that is the entrance of iron into the portal plasma?
Ferroportin
83
What is the name of the protein that allows for iron to exit the cell?
Ferroportin
84
What is unconjugated billirubin?
This is the bilirubin that cannot leak into urine, it is very large and also binded to a bilirubin binding protein
85
What are the different evidence of Haemolytic Anaemia?
1.Elevated bilirubin
2.Decreased haptoglobin
3.Elevated LDH
4.Elevated AST
5.Patient has Jaundice( Unconjugated hyperbilirubinemia)
6. Dark faeces
7.Increased reticulocytes
8.Increased urobilinogen in urine
9. Pigmented gallstones
86
What are the different branches of anemias?
1.Mircrocytic MCV less than 80 fL
2.Normocytic ( Haemolytic & Non hemolytic) 80-100 fL
3.Macrocytic more than 100 fL
87
At the end of their life cycle, where are red blood cells broken down?
In the macrophages of the reticuloendothelial system
88
What is the nature of a ferritin molecule?
It contains 22 sub units and a iron-phosphate-hydroxide -core
89
Describe Haemosiderin ?
* It is an insoluble protein–iron complex of varying composition containing approximately 37% iron by weight.
* It is derived from partial lysosomal digestion of ferritin molecules and is visible in macrophages and other cells by light microscopy after staining by Perls’ (Prussian blue) reaction
90
What is the name of the copper containing enzyme that catalyses oxidation of the iron TO the ferric form in order to be binded to plasma transferrin?
Caeruloplasmin
91
True or False? Low concentrations of 2-3,DPG , H+ ions , Carbon dioxide and Hb S (Sicke cell anaemia ) will shift the Oxygen concentration curve to the right.
FALSE!! HIGH concentrations of all of these will shift the curve to the Right!!
92
What is Intravascular Haemolysis?
Intravascular Haemolysis is the breakdown of Red Blood Cells that occurs within the blood vessels/circulation.
93
What are the different evidences of Intravascular Haemolysis?
Gosh- Gall stones (chronic)
this
H- Haemoglobinuria. (chronic)
H -Haptoglobin decrease
H- Haemoglobinanaemia
H- Haemosiderinuria (chronic)
A- Acute tubular necrosis
A- AST increase
M- Methaemglobinaemia
M- Methaemalbuminaemia
Lunch - LDH Increase
is
Unbelievable - Urobilinogen in urine
"Gosh!!! this HHHHAMM Lunch is Really Unbelievable"
94
What is Extravascular Haemolysis
Extravascular Haemolysis is the breakdown of RBC's by macrophages of the Reticuloendothelial system in liver and spleen.
95
What are evidences of Extravascular Haemolysis?
L - LDH increase
U - Urobilinogen in urine
S - Spelenogamaly( MAIN ONE)
A- AST increase
R- Reticulocytosis
" I LUSAR than Lucy , I sweeter than Juicy "
96
What are the two products after the break down of haem?
Iron (Fe2+) and Protophyron
97
What are the three divisions of Intrinsic Haemolysis aka (Hereditary)
Defects in RBC Metabolism
Defects in Haemoglobin Structure, function and production
Defects in RBC membrane production
"HRR Defects"
98
Examples of Defects in RBC metabolism.
These are the E- Enzymes
P- Pyruvate Kinase deficiency
G - G6DP deficiency
Not" ECG "but "EPG" lool
99
Examples of Defects in Haemoglobin structure, function and production.
Some- Sickle Cell disease
Terrible- Thalassemia
Haemoglobin - HbC disease
"Some Terrible Haemoglobin"
100
Examples ofdefects of RBC cell membrane production.
Please - Paroxysmal nocturnal haemoglobinuria
Help - Hereditary elliptocytosis
Henry's- Hereditary spherocytosis
membrane
"Please Help Henry's membrane"
101
What are the causes of Hereditary Spherocytosis?
Extravascular haemolysis due to defect in proteins interacting with RBC membrane skeleton + plasma membrane.
These proteins are: BAPS - Band 3 protein, Ankyrin, Paladin, Spectrin(alpha &beta)
Results: small , round RBC with no central pallor.
102
What are the clinical finding asscociated with Hereditary sperocytosis?
1. Splenegomaly
2. Aplastic crises ( Parovirus B19) infection
Test: Eosin malemide (EMA ) binding test
103
How does one treat Hereditary Spherocytosis?
Splenectomy
104
What is Hereditary Elliptocytosis?
This is a failure of spectrum heterodimers to self associate into heterotetramers . Patients with this may also present with severe haemolytic anaemia aka hereditary pyropoikilocytosis.
105
What is South East Asian Ovalocytosis?
This is caused by a nine amino acid deletion at the junction of they cytoplasmic and transmembrane domains of the band 3 protein.
106
True or false? A deficiency in G6DP mostly affects females and is carried by males?
FALSE!! It mostly affects MALES and is carried by females.
X-linked recessive
107
What are some causes of Intravascular heamolysis
1. Mismatched blood transfusion
2.G6PD deficiency with oxidant stress
3.Red cell fragmentation syndrome
4.Some severe autoimmune haemolytic anaemia
5.Drug infected - drug Induced Haemolytic anaemia
6.Paraoxysmal nocturnal haemoglobinuria
7.March haemoflobinuria (
characterised by long walking/ running ~ might have this tbh lol)
8. Unstable haemoglobin
9.G6PD
108
What are the different causes for a G6PD deficiency?
Infections and other acute illnesses ex diabetic ketoacidosis
Drugs
Antimalarias(chloroquine)
Sulphonamides and sulphites
Other antibacterial agents
Analgesics ex aspirin
Antihelminths
Vitamin K analogues, Naphthalene, Probenecid
Fava Beans (Vica fava) contains Divicine- oxidant compound
109
What are the clinical findings associated with G6PD deficiency?
1.Back Pain
2.Haemoglobinuria
3.Neonatal jaundice
4. Non-spherocytic haemolytic anemia (rare)
5. Lab results - bite cells and Heinz bodies
"Stress makes me bite fava beans with Heinz ketchup"
110
What can a defect in the Embden-Meyerhof pathway lead to?
Non spherocytic anaemia
111
Which test can be used to determine G6PD deficiency and Pyruvate Kinase Deficiency
Direct Enzyme Assay
112
What are the features of Pyruvate Kinase deficiency?
The red blood cells become rigid because of a reduced ATP leading to extravascular haemolysis. There is also an increase in the 2,3-DPG enzyme so Oxygen affinity decreases .
113
What are the clinical features of Pyruvate Kinase deficiency?
- Autosomal recessive
-Jaundice
- Gall stones
-Prickle cells
-Poikilocytosis (an increase in abnormal red blood cells of any shape that makes up 10% or more of the total population.)
114
What are the different types of Extrinsic (Acquired ) Haemolytic anaemia?
Autoimmune: Warm type Anitbodies & Cold type antibodies
Alloimmune
Red Cell fragmentation syndromes
March haemoglobinuria Infections (malaria,clostrida, babesia)
Chemical and physical agents (Drugs, Industrial/domestic substances, burns)
Secondary Diseases (liver & renal disease)
PNH
115
What are autoimmune haemolytic aneamias?
Autoimmune haemolytic anaemias (AIHAs) are caused by antibody production by the body against its own red cells. They are characterized by a positive direct antiglobulin test (DAT), also known as the Coombs’ test ) and divided into ‘warm’ and ‘cold’ types (Table 6.5) according to whether the antibody reacts more strongly with red cells at 37°C or 4°C.
116
What is the lifespan of platelets?
10 days
117
What is the lifespan for monocytes?
20-40hrs
118
What is the lifespan of Neutrophils in the blood?
6-10hrs
119
Where is thrombopoeitin made?
In the liver
120
Which immunoglobulin is used to coat RBC's in Warm haemolytic anaemia?
Immunoglobulin G (IgG)
"WARM weather is Great"
121
What type of antibody does RBC's bind to in cold autoimmune haemolytic anaemia?
IgM
" Cold weather is MMMiserable "
122
In which diseases are the antibodies monoclonal?
1. Primary cold haemagglutinin syndrome
2. Lymphoproliferative disorders such as Chronic lymphocytic leukaemia (CLL)
123
In which diseases are the antibodies transient polyclonal?
Infectious Mononucleosis
Mycoplasma pneumonia
" Cold weather is MMMiserable "
124
What laboratory findings would occur in a patient with Warm Autoimmune haemolytic anaemia?
Spherocytes on peripheral blood smear
Positive Direct antiglobin test (DAT)
125
What temperature are the antibodies presented in Warm AIHA ?
37°C.
126
What are some clinical features of Warm AIHA?
1.Splenegomaly
2.Evan's syndrome ( Warm AIHA + idiopathic thrombocytopenic purpura (ITP)
127
What are the RBC's coated with in warm AIHA when secondary to SLE?
Immunoglobulins and complement
128
At what temperature will IgM antibodies bind to RBC's optimally?
4°C
129
True or false?
Only complement factors can be detected on red cells in laboratory tests as the IgM antibody is eluted off as cells flow through warmer parts of the circulation.
TRUE!!!
130
What is Primary Cold Agglutinin disease?
This is when the patient has a chronic haemolytic anaemia aggravated by the cold and often associated with intravascular haemolysis.
131
What are the clinical features of Primary cold agglutinin disease?
Mild jaundice
Splenomegaly
Acrocyanosis ( Purplish colour on skin)
Red cell agglutination present
Only complement C3d present.
132
What is alloimmune haemolytic anaemia?
In these anaemias, antibody produced by one individual reacts with red cells of another.
133
What are the three mechanisms through which Drug induced haemolytic anaemia can arise?
1.Antibody directed against a drug–red cell membrane complex (e.g. penicillin, ampicillin); this only occurs with massive doses of the antibiotic.
2.Deposition of complement via a drug–protein (antigen)– antibody complex onto the red cell surface (e.g. quinidine, rifampicin); or
3. A true autoimmune haemolytic anaemia in which the role of the drug is unclear (e.g. methyldopa).
In each case, the haemolytic anaemia gradually disappears when the drug is discontinued.
134
What is Hematocrit?
Hematocrit is the percentage by volume of red cells in your blood.
135
True or False? Intravascular Heamolysis plays little or no part in normal red cell destruction?
TRUE!!
136
What clusters of genes found on globin chains are found on chromosome 11?
ε, γ, δ and β Epsilon, Gamma, Delta and Beta
137
What number chromosome is ζ and α found ( Zeta and alpha) ?
Chromosome 16
138
At what position does the gamma chain differ at Gγ and Aγ (glycine and alanine)?
At position 136 on the polypeptide chain.
139
True or false? All globin genes have three exons(coding regions) and two introns ( non- coding regions whose DNA is not represented in the finished protein)
TRUE!! ( globin has 3 exes and two maIN men"
140
What sequence does the introns begin and end with?
Begin. - G-T dinucleotide
Ends: A-G dinucleotide
"beGin"
141
A defect in globin synthesis may give rise to what disease?
Thalassemia
Haemolysis
Ineffective erythropoiesis
142
What are the purposes of the sequences needed for globin synthesis?
It influences gene transcription, ensures fidelity, specify sites for the initiation and termination of translation and ensure the stability of newly synthesized mRNA.
143
What are important in tissue specific regulation of globin gene expression and in the regulation of synthesis of various globulin chains during metal and postnatal life?
Enahncers
144
Where are promoters found?
At the 5′ of the gene.
145
What is the locus control region (LCR)?
It is a genetic regulatory element, situated upstream of the β‐globin cluster, that controls genetic activity by opening up the chromatin to allow transcrip tion factors to bind.
146
When does the switch occur from fetal Hb to adult Hb?
3–6 months AFTER birth when synthesis of the γ chain is replaced by β chains.
147
What is a major transcriptional regulator of the switch from fetal Hb to adult Hb?
BCL11A
148
In what state is inorganic iron " non heme" ?
ferric, Fe3 + state ( coming from plants and has to be reduced to the Ferrous state, Fe2 +
149
Hb S, Hb C , Hb D and Hb E are as a result in substations of which chain?
Beta chain
150
Which thalassemia is more common in the Mediterranean region?
Beta Thalassemia
151
True or False? Alpha thalassemia is also common in the Mediterranean region?
FALSE!! They are more common in the Far East region
152
What are examples of Microcytic Anaemia?
T - Thalassemias
A- Anaemia of chronic disease
I- Iron deficiency
L- Lead poisoning
" Tail"
153
What are examples of Macrocytic Anaemia ?
Megaloblastic Non-megaloblastic
F- Folate Deficiency L- Liver disease
O- Orotic Aciduria A- Alcoholism
F- Fanconi Anaemia D- Diamand- Blackfan
V- Vitamin B-12 deficiency Anaemia
"FOF was Very LAD"
154
What are types of Non-haemolytic anaemia
C- Chronic Kidney disease
I- Iron deficiency
A-Anaemia of chronic disease
A- Aplastic Anaemia
155
True or False? Alpha thalassemia is not a disorder of ineffective erythropoiesis.
TRUE!!
156
What would be the best treatment for persons with HbH disease ( usually associated with 3 alpha gene deletion)?
Splenectomy - This is due to the fact that there is an increase in H (β4) in the blood which may result in the formation of Heinz bodies. These Heinz bodies are then cleared by the spleen resulting in Splenomegaly.
157
What are the clinical features associated with 4 alpha chain deletion Thalassemia?
1.Hydrops fetalis ( is a condition in which large amounts of fluid build up in a baby's tissues and organs, causing extensive swelling (edema).
2. Excess y4 formation
3. Foetus will die.
158
What are the clinical features associated with one alpha chain deletion in alpha thalassemia?
1.No symptoms present
2. Low MCV and MCH
3. Red cell count Is over 5.55 × 10 ^12/L.
159
What is another name for Beta Thalassemia major?
Cooley Anaemia
160
True or False? Persons with Beta thalassemia trait who have excess alpha genes tend to be less anaemic than usual?
FALSE!! They tend to be more anaemic than usual.
161
What is Haemoglobin Lepore?
This is an abnormal haemoglobin caused by unequal crossing‐over of the β and δ genes to produce a polypeptide chain consisting of the δ chain at its amino end and β chain at its carboxyl end.
162
What is a next name for Vitamin B12?
Cobalamin
163
Where is Intrinsic factor produced?
By the cardia and fundus and cardia of the stomach parietal cells
164
Where does Intrinsic factor plus B12 (IF-B12) bind to Cubulin?
In the ileum
165
What is the name of the compound to which vitamin b12 in the portal blood binds to?
Transcobalamin (TC, or Transcobalamin II)
166
Congenital Transcobalamin deficiency causes what disease?
Megaloblastic Anaemia
167
What is Haptocorin (transcobalamin 1 ) synthesised by?
Ganulocytes and Macrophages
168
What is the minimal daily adult requirement for Vitamin B12?
1-2 μg
169
What is the daily adult requirement for folate?
100–150 μg
170
What is the function of the second protein Aminionless in the B12 absorption?
It directs endocytosis of the cubilin IF–B12 complex in the ileal cell so that B12 is absorbed and IF destroyed
171
Why is the B12 levels in serum in TC deficiency normal than that of the b12 levels in blood plasma in TC deficiency low?
This is because B12 in serum binds to Haptocorin ( also called Transcobalamin 1) which is different than that of B12 in blood plasma which binds to Transcobalamin II aka TC aka Transcobalamin)
172
What is the body stores in Folate?
10-12 mg (sufficient for 4 months)
173
What is the body store of B12 ?
2-3 mg ( sufficient for 2-4 years)
174
What is the range that B12 binds to TC?
Normally Very low (<50ng/L).
175
Where is vitamin B12 absorbed in the body?
Ileum
176
Where is folate absorbed in the body?
Duodenum and Jujenum ( Mainly Jujenum)
177
True or False? Cooking has a great effect on Vitamin B12 ( it is easily destroyed?
FALSE!! Cooking has little effect on vitamin B12 it has a GREAT effect on FOLATE ( it is easily destroyed)
178
What are dietary sources for folate?
Dark green leafy vegetables, yeast, liver etc
179
True or false? Folate is weakly bound to albumin?
TRUE!!
180
What is the form in which folate is circulated in plasma?
Methyltetrahydrofolate (methylTHF)- a reduced monoglutamate!!
181
A deficiency in folate and vitamin B12 is said to cause?
Megaloblastic Anaemia
182
What is the normal dietary intake for folate?
200-250 μg
183
What is the physiological dietary folate need for women who are pregnant?
600mcg
184
What is the stable form of Vitamin B12 ?
Cyanocobalamin
185
What condition does vitamin b12 absorption take place in?
Acidic conditions - pH 5.4
186
What is another name for Transcobalamin 1?
TC 1, Haptocorin, R-protein
187
What is the function of Haptocorin?
To protect Cobalamin from acidic environments of the GI tract
188
Where are Transcobalamins III found?
In neutrophils
189
Where are transcobalamins II synthesised?
They are synthesised by monocytes, endothelial cells, epithelial cells.
190
Where is Haptocorin located?
In monocytes, mature granulocytes, exocrine epithelial cells in Saliva, gastric acid, bile and breast milk.
191
Where is Folate stored?
In the liver
192
True or False? Aplastic crisis results in a fall in the Hb levels and a rise in the reticulocyte count.
FALSE!! Aplastic crises results in a fall in the Hb levels and a FALL in the reticulocyte count !! Haemolytic crises results in a fall in Hb and a RISE in reticulocyte count.
193
True or false? Peripheral neuropathy is a sign/symptom of vitamin B12 AND folate deficiency?
FALSE!! Peripheral neuropathy is ONLY a sign/symptom of vitamin B12 deficiency.
194
What is pancytopenia?
This is a condition in which there is a lower-than-normal number of red and white blood cells and platelets in the blood.
195
What causes rapid inactivation of body B12 by oxidizing the reduced cobalt atom of methyl B12?
Nitrous Oxide
196
True or False? In folate deficiency there is an INCREASE in homocysteine and an NORMAL level of Methylmalonic acid?
TRUE!!
197
In Vitamin B12 deficiency what are the laboratory findings
1) Decreased Hb and Hct
2) MCV is increased
3) Peripheral blood smear shows pancytopenia, oval macrocytosis, hypersegmented neutrophils
4) INCREASED levels of homocysteine AND methylmalonic acid
198
What is Diamond - Blackfan anaemia?
It is s a rare inherited congenital erythroid aplasia that normally presents within the first year of life. It is characterized by a defect leading to a decrease in erythroid progenitor cells in the bone marrow. CF- triphalangeal thumb ( thumb looks like a regular finger, elevated HbF ,
199
What is the main distinction between Megaloblastic anaemias and non megaloblastic anaemias?
Megaloblastic has hypersegmented neutrophils while non megaloblastic has no hypersegmented neutrophils
200
In a congestive state of splenomegaly, what are the findings?
Marked enlargement
Firm(cricket ball)
Histology
- Gamma Gandy bodies
- Fibrosis
- Infarcts
- Extramedullary haemopoesis
201
In a haematological state (sickle cell disease)of splenomegaly, what are the findings?
1. Gamma Gandy bodies
2. Congestion of splenic cords
3.Depressed scars
4. Repeated hemorrhagic infarction
5. Sequestration ( in childhood)
6. Autosplenctomy ( in puberty)
202
In relation to Splenomegaly, In which disease would you find Erythrophagocytosis?
Typhoid fever
203
In relation to Splenomegaly, In what disease would you see Mononucleosis?
EBV ( Epstein-Barr Virus)
204
What are the clinical findings in Splenomegaly due to Infections?
1.Moderatley Enlarged
2. Very soft, semi- liquid ,diffluent(mushy)
3. Congested
205
What are sone examples of Autoimmune diseases that can cause Splenomegaly?
Rheumatoid Arthritis(RA)
Amyloidosis
Sarcoidosis
Systematic Lupus Erythematosus (SLE)
"RASS"
206
True or False? Folate is needed to convert Serine to Glycine
TRUE!!
" F Serena in gossip girl"
207
What enzyme would be inhibited in B12 deficiency?
Thymidylate synthase
208
What are the clinical findings in Splenomegaly due to AI diseases?
Marked to moderatley enlarged
Prominent White pulp
White pulp hyperplasia
209
What are the causes of Massive splenomegaly?
chronic Myeloid leukaemia
Malaria
Myelofibrosis
"The three M's"
210
What may be the cause of a splenic cyst?
Parasitic ( Echinococus -dog-tape worm- hyatid cyst)
Non -parasitic
True cyst
- Epidermoid , dermoid
Pseudo - cyst
- Trauma, haemorrhage and organisation
211
What is the origin for True cysts?
Epithelial lining
212
What is the origin for pseudo cysts?
Fibrous tissue lining
213
In which organs would a haemorrhagic (red) infarction take place (dual circulation)?
Lungs
Small Intestine
214
In which organs would an anaemic (white) infarction take place (arterial circulation) ?
Heart
Spleen
Kidney
215
What is Anisocytosis?
A variation in the SIZE of red blood cells
216
What is as a result in the variation of the SHAPE of a red blood cell?
Poikilocytosis
"shaPe"
217
What are basophils commonly associated with?
They are commonly involved with inflammatory reactions that cause allergic symptoms. They express immunoglobulin E (IgE) receptors that release histamine, heparin, prostaglandins, leukotrienes, and other vasoactive amines when stimulated
218
True or False? The Mean Corpuscular Haemogobin Concentration (MCHC) is decreased in all Microcytic Anaemia?
TRUE!!
219
An elevated MCHC levels can indicate which disease?
Hereditary Spherocytosis
220
What is Hypochromia?
Poor haemoglobinisation (low MCH), increased central area of pallor
221
What are some examples of Immature white blood cells?
Bands, Metamyelocytes, myelocytes, promyelocytes,and promyeloblasts
They cause a Left shift.
222
What is the normal red cell count in men and women?
Men - 5.5 x 1.0 x10^12
Women- 4.8 x 10^12
223
What is Hypo- regenerative anaemia?
This is Anaemia plus a low reticulocyte count . The RPI is less than 2 .
This indicates that there is bone marrow failure
224
What is Hyper -regenerative anaemia?
This is Anaemia + a high reticulocyte count. The RPI is more than 3 .
This indicates an increase in red cell destruction or consumption with a concomitant increase in red cell production.
225
What is the normal reticulocyte count in Adults and children ?
0.2- 2%
226
True or false? A decrease in Oxygen stimulates Erythropoesis?
TRUE!! while A increase in oxygen depresses it.
227
True or False?An appropriate bone marrow response to anemia would result in a corrected reticulocyte count greater than 3%
TRUE!!
228
What is the normal MCV in adults ?
80-100 ( 85 +/- 8 fL)
229
What is the normal MCH in adults?
29.5 +/- 2.5 pg
230
What is the normal MCHC in adults and children?
33 +/- 2 g/dl
231
True or False? There is an increased reticulocyte count in Iron Deficiency Anaemia.
FALSE!!! The reticulocyte count is DECREASED!!
232
True or False? There is an increased Reticulocyte count in Megaloblastic Anaemia?
FALSE!!The reticulocyte count is DECREASED!!
233
True or False? Filtration is more efficient than washing in removing leukocytes.
TRUE!!
234
Fill in the blank "_________ CANNOT remove cytokines."
Filters
235
At what temperature is Packed red cells and whole blood stored at ?
1-6 degrees Celcius
236
True or False? Irradiation of red cells is not indicted for immunodeficient patients.
FALSE!! It IS indicated
237
At what temperature is Fresh Frozen plasma stored and how long does it last?
-30 degreed Celsius and lasts 12 months in the blood bank
238
What is the difference between Fresh Frozen Plasma and Stored plasma?
FFP contains ALL clotting factors while Stored plasma DOES NOT contain all clotting factors.
239
True or False? Platelets transfusion can be used to treat TTP.
FALSE!! It will make the condition WORSE!!
240
What two brand groups are Leucocytes divided into?
Phagocytes and Immunocytes
241
What are type of phagocytes?
1)Granulocytes
- Eosinophil
- Basophil
- Neutrophil
2) Monocytes
242
Which substances act locally on the pluripotential stem cells and on early myeloid and lymphoid progenitor?
SCF and FLT3 ligand (FLT3‐L)
243
Fill in the blanks. " Cytokines _________ and _________can exert a negative effect on haemopoiesis and may have a role in the development of aplastic anaemia."
Transforming growth factor‐β (TGF‐β) and γ‐interferon (IFN‐γ)
244
Which growth factors act on Stromal cells?
IL-1 & TNF
245
Which growth factors act on Pluripotent stem cells?
SCF
FLT3‐L
VEGF
246
Which growth factors act on multipoint stem cells?
IL‐3
GM‐CSF
IL‐6
G‐CSF Thrombopoietin
247
Which growth factors act on committed progenitor cells?
G‐CSF*
M‐CSF
IL‐5 (eosinophil‐CSF)
Erythropoietin
Thrombopoietin*
248
A mutation of which gene can cause polycythaemia rubra vera?
JAK2 gene
249
What is the function of p53?
It plays a role in sensing DNA damage. It activates apoptosis by raising the cell level of BAX which then increases cytochrome c release (Fig. 1.9). P53 also shuts down the cell cycle to stop the damaged cell from dividing .
250
By what protein is p53 controlled by?
MDM2 protein
251
How many mature red blood cells does one pronormoblast produce?
16 mature red blood cells
252
True or False? Reticulocytes contain nuclear DNA.
FALSE!! They contain RNA in their cytoplasm.
253
True or False? Normoblasts are NOT present in the normal human peripheral blood. If they are present , it is an indication that erythropoiesis is occurring outside the marrow (extramedullary erythropoiesis) and also with some marrow diseases.
TRUE!!
254
Which enzyme is a coenzyme in Haemoglobin synthesis ?
Pyridoxal phosphate (vitamin B6 )
255
From which cells do the Steel Factor(Stem Cell factor- SCF) originate from?
From stromal cells in bone marrow
256
What is the diameter of pluripotent stem cells?
18-23 μ
257
What are the functions carried out by White blood cells?
- Phagocytosis
- Macrophage action
- Amoeboid action
- Chemotaxis
- Diapedesis
258
In Neutrophils, the primary granules appearing at PROMYELOCYTE stage ( of lysosomal origin) contains what substances?
- Myeloperoxidase
- Acid Phosphatase
- Proteinase
- Beta -glucuronidase
- Other acid hydrolases
259
In Neutrophils, the secondary granules appearing at the MYELOCYTE stage contains what substances?
- Collagenase
- Lacto ferrin
- Leukocyte alkaline phosphatase (LAP)
- Lysozyme
260
What is the lifespan of neutrophils in blood?
6-10 hrs
261
How can the nucleus of an Eosinophil be described?
Bi-lobed
262
Fill in the blanks, Eosinophils has coarse granules containing _______, _______, ________ & _______"
Major basic protien
Lysosomal enzymes
Plasminogen
Histamine
263
What substances are produced in the granules of Basophils?
Serotonin
Heparin
Histamine
264
What immunoglobulin does Basophils have attachment sites for?
IgE antibodies
265
True or False? When ferritin stores are decreased, the liver synthesizes more transferrin however while when ferritin stores are high, the liver decreases the production of transferrin.
TRUE!!
266
What is the volume of capacity in which Transferrin can absorb iron?
300 μg/dL
267
Which two acids are important in iron absorption?
Gastric Acid (HCl )
Ascorbic acid ( Vitamin C)
268
True or False? Iron deficiency and Primary hemochromatosis reduces iron absorption.
FALSE!! They INCREASE iron absorption.
Iron deficiency favours iron absorption because when the iron stores are depleted the rate of absorption isaccelerated.
Primary Hemochromatosis
269
Fill in the blanks."_________ , the absence of stomach acid decreases the amount of iron available for reabsorption.
Achlorhydria
270
What are some examples of Heme enzymes?
Catalase, cytochromes, peroxidase, flavo protein
271
By what process , is iron bounded to transferrin absorbed into the epithelial cells and then released into blood capillaries to form plasma transferrin?
Pincytosis
272
At what stage does team synthesis begin?
Pro-erythroblast stage
273
Where are global chains synthesised?
On ribosomes in cytoplasm
274
True or False? 4 heme + polypeptide = haemoglobin chain.
TRUE!!!
275
True or False? In haemoglobin synthesis, Each heme molecule combines with a globin chain .Forming a tetramer of four globin chains each with its own heme group in a pocket which creates a hemoglobin molecule.
TRUE!!!
276
In Sickle cell anaemia, HBSS what substitution occurs?
A point mutation in the β-globin gene substitutes Glutamic acid with Valine at position 6
277
What is the importance of ATP, in red cell metabolism using the hexose-monophosphate shunt?
It provides energy needed for:
- Maintenance of red cell volume
- Maintenace of cell shape/flexibility
- Membrane ATPase sodium pump
278
What is the test used to detect Hereditary Spherocytosis?
Osmofragillity Test
279
What are causes of Vitamin B12 deficiency?
*Achlorhydria
*Lack of IF, gastric or ileal resection (ileum needed for absorption of cobalamin)
*Crohn disease or celiac disease in the terminal ileum
* Insufficient dietary intake ( seen in vegetarians)
*Diphyllobothrium latum (fish tapeworm)
*Pancreatic insufficiency
*Pernicious anemia
* Pregnancy
* Hyperthyroidism
280
What is the body store of Folate( Via B9)?
10-12 mg (sufficient for 4 months)
281
What is the body store of Vitamin B12?
2-3 mg ((sufficient for 2–4 years)
282
What protein does Folate bind to?
It weakly binds to Albumin
283
What is the normal dietary intake of Vitamin B12?
7–30 μg
284
What is the normal dietary intake of Vitamin B9?
200–250 μg
285
What is the ratio contained in red cell membranes?
50% of membranes is proteins
20% of membrane is phospholipid
20% of membrane is Cholesterol
10% of membrane is Carbohydrate
286
What are the proteins that make up the red cell membrane?
α and β spectrin
Ankyrin
Protein 4.1
Actin.
287
What is the most abundant protein found in the Cell membrane?
Spectrin
