blood Flashcards
Which of the following correctly describes the changes in hemoglobin composition during human development?
A) HbA2 levels increase significantly after birth, becoming the dominant form in adults.
B) HbF (fetal hemoglobin) predominates in fetal life but decreases after birth, replaced mostly by HbA (adult hemoglobin).
C) HbF levels remain constant throughout life, while HbA only appears in late childhood.
D) HbA is the dominant form in fetal life, while HbF becomes the primary form in adulthood.
B) HbF (fetal hemoglobin) predominates in fetal life but decreases after birth, replaced mostly by HbA (adult hemoglobin).
Alpha Always, (α)
Gamma Goes, (γ)
Becomes Beta (β)
=> HbF (α2γ2) predominant form during fetal form and decline after birth,
and HbA (α2β2) becomes the dominant form instead
definition of anemia
decrease in Hb
and/or decrease in RBC
how does anemia lead to fatigue
low Hb and/or RBC
[definition of anemia]
-> low oxygen-carrying capacity
-> hypoxia
-> lower rate of aerobic resp
-> less ATP released
=> fatigue
3 types of anemia
(based on MCV)
- microcytic = decreased MCV
- normocytic = normal MCV
- macrocytic = increased MCV
cause of microcytic anemia
insufficient/abnormal Hb synthesis,
usually due to iron deficiency
OR thalassemia
2
causes of normocytic anemia
- increased RBC destruction
a. blood loss
b. haemolysis - decreased RBC production
a. kidney damage -> decreased EPO production
b. anemia of chronic disease -> suppress EPO production
erythropoietin (EPO) signals bone marrow to produce more RBCs,
is produced by kidney
and is increased in response to drop in pO2
cause of macrocytic anemia
impaired DNA synthesis and cell div,
usually due to vitamin B12 or folate deficiency
when is erythropoietin (EPO) produced
when there is low O2 levels (hypoxia)
-> stimulates bone marrow to increase RBC production
=> increase O2 delivery to tissues
produced by kidneys
what will ferritin levels be like in iron-deficiency anemia
low
<- depleted iron stores
ferritin stores iron
what will
transferrin levels, transferrin saturation and total iron binding capacity (TIBC)
be like in iron deficiency anemia
liver increases transferrin production
to maximise iron transport
=> high levels of transferrin
thus more available binding sites for iron
=> high TIBC
however less iron available to bind transferrin
=> low transferrin saturation
in which scenario will there be LOW reticulocyte count?
A) Folate or B12 deficiency
B) Hemolytic anemia
C) Acute blood loss
A) Folate or B12 deficiency
-> impairs DNA synthesis
-> premature destruction of RBC precursors in the bone marrow before they can mature into reticulocytes and be released
(intramedullary hemolysis from ineffective erythropoiesis)
=> fewer reticulocytes released
Reticulocytes are immature RBCs released by bone marrow into bloodstream
high reticulocyte count = increased production of RBCs by bone marrow as COMPENSATION
for (B), compensating for RBCs which are destroyed in circulation
for (C), compensating for RBCs lost through blood loss
early/late, any cons
comment on ferritin levels as indicator of iron deficiency
- good as earliest indicator of iron deficiency
- bad as inflammation or infection can also increase ferritin levels
<- ferritin is acute-phase reactant
increased production of ferritin during inflammation/infection
to sequester iron away from pathogens which need it to grow
difference in site of bleeding
in platelet disorders vs coagulation factor disorders
- platelet disorders: skin, mucous membranes (e.g. gum, epistaxis)
- coagulation factor disorders: deep soft tissues (joints, muscles)
which is the intrinsic pathway?
aPartial Thromboplastin Time (aPTT)
or Prothrombin Time (PT)
aPTT
Table Tennis is played indoors,
while extrinsic pathway is PT as Tennis is played outdoors
clotting pathway
What are the coagulation factors involved in common pathway
Factor I, II, V and X
bcos 1 x 2 x 5 = 10
clotting pathway
What are the coagulation factors involved in intrinsic pathway
Factors VIII, IX, XI and XII
bcos count down from 12 to 8
but exclude 10 as it is alr in common pathway
clotting pathway
What are the coagulation factors involved in extrinsic pathway
Factor VII
Hemophilia A and Hemophilia B are caused by deficiencies in which clotting factors?
A) Factor VII & Factor IX
B) Factor VIII & Factor IX
C) Factor V & Factor X
D) Factor VIII & Factor X
B) Factor VIII & Factor IX
Haemophilia A = Haemophilia Ate (8)
Haemophilia B = B is 1 letter after A = 9 (1+8)
Which does Haemophilia A and B affect,
aPTT or PT?
aPTT
as factors VIII (Haem A) and IX (Haem B) are both part of intrinsic pathway
recall!
factors in intrinsic pathway is 12 -> 8 (except 10)
intrinsic pathway is aPTT as Table Tennis is played indoors
Why does a deficiency of Factor VIII or IX lead to impaired clotting?
A) They directly convert fibrinogen to fibrin
B) They are necessary for the activation of Factor X in the coagulation cascade
C) They prevent platelet aggregation
D) They break down fibrin clots
B) They are necessary for the activation of Factor X in the coagulation cascade
Factor VIII (Haem A) and Factor IX (Haem B) are part of the intrinsic pathway
-> Factor X cannot be activated without them
-> no Factor X to activate thrombin
=> impaired clot formation
recall!
factors in intrinsic pathway are 12 -> 8 (except 10)
factors in common pathway are 1 x 2 x 5 = 10
implication!
since Factors VIII and IX are part of intrinsic pathway,
aPTT is affected in Haem A and B!
(aPTT = Table Tennis is played indoors)
What factors will be deficiency if there is a Vitamin K deficiency?
- Factor II (prothrombin)
- Factor X
- Factor VII
- Factor IX
as Vit K act as a cofactor for the carboxylation and thus activation of these factors
Which does Vit K deficiency affect,
aPTT or PT?
Both!
Factor IX is from intrinsic pathway,
(countdown from 12 to 8, exclude 10)
Factor VII is from extrinsic pathway
the remaining Factors II and X are from common pathway
(1 x 2 x 5 = 10)
What factors will be deficiency if there is liver disease?
All factors except Factors III and IV
as liver produces most clotting factors
Factor VI does not exist!
Factor III = tissue factor
-> produced by tissues when damaged and initiates extrinsic coagulation pathway
Factor IV = Ca2+
-> coemes from diet and bones
and essential for several steps in clotting pathway
Which does liver disease affect,
aPTT or PT?
Both!
Since all factors involved will be deficient
Why does Hemophilia (A and B) NOT cause excessive bleeding from small cuts but leads to joint and deep tissue bleeding?
A) The vascular response is unaffected
B) Platelets function normally
C) The coagulation cascade defect mainly affects fibrin clot formation
D) All of the above
D) All of the above
Hemophilia does not affect platelets
-> normal primary hemostasis (initial plug formation)
but results in deficiency of Factor VIII or IX
-> defective clot stabilization (secondary hemostasis)
=> deep bleeding (joints, muscles, GI tract, brain, etc.)
platelet count (PC), bleeding time (BT), PT or aPTT
what does vWF disease affect
- increases BT
as defect in platelet adhesion to exposed collagen - increases (or no change in) aPTT
<- decreased levels of Factor VIII
<- vWF stabilises Factor VIII
“volksWagen Factories make gr8 cars”
usually,
vWF binds to exposed subendothelial collagen at sites of vascular injury
-> platelets adhere to vWF via their GPIb receptor
=> platelet plug formation
recall! intrinsic pathway = aPTT as table tennis is played indoors
and it involves factors 12 -> 8 (exclude 10)
Which of the following best describes the underlying mechanism of Disseminated Intravascular Coagulation (DIC)?
A) Isolated platelet destruction leading to thrombocytopenia
B) Widespread activation of the coagulation cascade, leading to thrombosis and depletion of clotting factors
C) Overproduction of clotting factors without platelet involvement
D) Deficiency of von Willebrand Factor leading to abnormal platelet adhesion
B) Widespread activation of the coagulation cascade, leading to thrombosis and depletion of clotting factors
Trigger (e.g. sepsis, trauma)
-> excessive release of TF
-> activation of extrinsic pathway
-> widespread clotting
-> depletion of platelets and clotting factors
=> increased bleeding risk
are D-dimer levels increased or decreased in DIC
increased
D-dimer are fibrin degradation products
-> excessive clots broken down
=> increase in D-dimer
how does DIC affect PC, BT, PT and aPTT
- decreases PC
<- depletion of platelets for excessive clot formation - increases BT
<- less platelets to form clots and stop bleeding - increases PT and aPTT
<- depletion of platelets for excessive clot formation
mechanism of Factor V Leiden
mutated form of Factor V
-> resistant to degradation by APC/S complex
-> more prothrombin is converted to thrombin
-> excessive clot formation (hypercoagulability)
=> increased risk of DVT/PE
what does Tissue Factor Pathway Inhibitor (TFPI) do
regulates extrinsic pathway of coagulation
by inhibiting Tissue Factor-Factor VIIa (TF-FVIIa) complex
aPTT and PT
do heparin and warfarin affect diff timings
Heparin prolongs aPTT
* as it primarily affects factors in common and intrinsic pathways (XII, XI and IX)
while Warfarin prolongs PT
* as it FIRST affects extrinsic pathway
<- Factor VII has the shortest half-life
What is the primary purpose of a mixing test in coagulation studies?
A) To differentiate between clotting factor deficiency and the presence of an inhibitor
B) To measure the overall platelet count
C) To diagnose thrombocytopenia
D) To assess fibrinogen levels
A) To differentiate between clotting factor deficiency and the presence of an inhibitor
if clotting time corrects
=> clotting factor deficiency
if clotting time remains prolonged
=> factor inhibitor present
Process:
1. patient’s plasma + normal plasma mixed together in 1:1 ratio
2. clotting test is repeated
the types and how many gene copies each have
types of thalassemia
- Alpha thalassemia: 4 gene copies
(bcos each person has 4 α-globin gene copies)
4 mutations = fatal - Beta thalassemia: 2 gene copies
(bcos each person has 2 β-globin gene copies)
symptoms of thalassemia
- jaundice, anemia and splenomegaly
bcos excess β or α chains
-> HbH (β4) or toxic aggregates
-> premature destruction (haemolysis)
=> excessive RBC breakdown - target cells
bcos decreases α or B globin chain production
-> low Hb content (hypochromia)
-> more membrane relative to Hb
=> cell membrane folds on itself
In fetuses,
4 α-globin gene mutations
-> excess γ chains
-> Hb Barts (γ4)
-> higher oxygen affinity than HbH
-> cannot release O2 to fetal tissues
=> severe hypoxia and hydrops fetalis
name of enzyme, requires/inhibited by, clinical implication
1st enzyme in heme synthesis
ALA synthase 2
* needs B6
* inhibited by heme and iron
name of enzyme, requires/inhibited by, clinical implication
2nd enzyme in heme synthesis
ALA dehydratase
* inhibited by lead
* lead poisoning
-> bluish line on gums
name of enzyme, requires/inhibited by, clinical implication
3rd enzyme in heme synthesis
Uroporphyrinogen decarboxylase
* affected in porphyria cutanea tarda
-> red urine, photosensitivity
name of enzyme, requires/inhibited by, clinical implication
4th enzyme in heme synthesis
Ferrochelatase
* inhibited by lead
* lead poisoning
-> bluish line on gums
how does heme → bilirubin (unconjugated)
heme → biliverdin → bilirubin
in macrophages
how is bilirubin transported in bloodstream?
A) Bound to transferrin
B) Bound to albumin
C) In free form as unconjugated bilirubin
D) Bound to hemoglobin
B) Bound to albumin
unconjugated bilirubin is insoluble
→ binds to albumin for transport to liver
during heme breakdown
what happens in the liver
bilirubin conjugation occurs
-> making it soluble
what are the 2 pathways of conjugated bilirubin in liver
upon secretion into bile
and conversion nto urobilinogen in gut,
1. some are oxidised to stercobilin
-> excreted in feces
=> give feces its brown colour
2. others are reabsorbed by liver
-> transported to kidneys
-> converted to urobilin
-> excreted in urine
=> giving urine its yellow colour
signs of haemolysis
- rise in LDH
bcos it’s an enzyme found in RBC - rise in unconjugated bilirubin
due to RBC breakdown - decrease in haptoglobin
bcos haptoglobin binds to free Hb
-> RBC breakdown
-> more Hb
-> more haptoglobin binding to Hb
what causes prehepatic jaundice
too much Hb breakdown
-> too much heme
bilirubin, urine, lab levels
findings in prehepatic jaundice
- increase in unconjugated bilirubin
- normal urine
OR (if severe) dark urine
<- too much Hb to be broken down, thuss excreted instead - decrease in haptoglobin levels
<- haemolysis
what causes post hepatic jaundice
something which obstructs bile FLOW,
usually bile duct OBSTRUCTION
bilirubin, urine, lab levels
findings in post hepatic jaundice
- increase in conjugated bilirubin
-
tea coloured urine
cos bile flow is obstructed
-> conjugated bilirubin backs up into bloodstream
-> eventually excreted by kidneys - increase in ALP and GGT levels
cos bile flow is obstructed
-> bile buildup and subsequent damage to bile duct cells
=> release of enymes into bloodstream
types of hepatic jaundice
- defect in conjugation:
(similar to prehepatic jaundice) increase in unconjugated bilirubin - defect in excretion
(similar to post hepatic jaundice) increase in conjugated bilirubin - mixed defect
think abt word HEPATIC
findings in hepatic jaundice
- increase in AST and ALT levels
cos liver damage
-> leakage of liver enzymes into bloodstream - decreased liver fuction
-> decreased albumin (impaired protein synthesis)
-> increased clotting times, aPTT and PT (impaired clotting factor synthesis)
1st child, 2nd child
haemolytic disease of newborn
(Rh incompatibility)
- Sensitisation
1st child has RhD antigen
(inherited from father, mother doesn’t have)
-> causes mother to produce antibodies against RhD - Next fetus
Mother’s anti-RhD antibodies cross placenta
-> bind to RhD antigen on RBC of 2nd Rh+ child
treatment for haemolytic disease of newborn
(Rh incompatibility)
anti D injection
where body will treat ANY fetal RBCs that cross over as foreign and eliminate it
-> mother does not sensitise against RBCs w/ RhD antigen
what is added to blood plasma samples when measuring aPTT
-
Kaolin
-> activates clotting factors (in intrinsic pathway) - Ca2+
-> activates clotting factors (in coagulation cascade in general) - phospholipids
-> mimic cell membrane envt
what is added to blood plasma samples when measuring PT
thromboplastin
-> TF and thus activates extrinsic pathway
Virchow triad consists of …
Hypercoagulability
Endothelial damage
Stasis
“HE‘S Virchow”
one risk factor of endothelial damage is smoking,
but NOT alcohol!
What is the main protein responsible for iron storage in cells?
A) Transferrin
B) Ferritin
C) Haptoglobin
D) Hemosiderin
B) Ferritin
primary and most abundant storage of iron
in contrast, hemosiderin stores iron during iron overload
What is the primary protein responsible for transporting iron in the bloodstream?
A) Ferritin
B) Transferrin
C) Hemoglobin
D) Myoglobin
B) Transferrin
binds to iron in Fe3+ state
thus iron is oxidised from Fe2+ to Fe3+ by hephaestin beforehand
Which form of iron is absorbed most efficiently by the body?
A) Ferric iron (Fe³⁺)
B) Ferrous iron (Fe²⁺)
C) Iron bound to heme
D) Iron bound to transferrin
B) Ferrous iron (Fe²⁺)
thus iron is absorbed as Fe2+ into intestinal cells by DMT,
then reduced to Fe3+ by ferric reductase in cell
What enhances the absorption of non-heme iron from the diet?
Vitamin C
non-heme iron is usually in Fe3+ form
→ Vit C helps to reduce Fe3+ to the more absorbable Fe2+
What is the role of hepcidin in iron regulation?
A) It promotes the absorption of iron from the intestines
B) It prevents the release of iron from enterocytes into the bloodstream
C) It increases the synthesis of ferritin
D) It binds to transferrin to transport iron
B) It prevents the release of iron from enterocytes into the bloodstream
hepcidin binds to ferroportin,
causing its internalisation and degradation
→ inhibit release of iron from enterocytes into bloodstream
hepcidin is a hormone produced by liver to control iron levels
⇒ high iron levels = more hepcidin
What is the body’s response to a low iron state
- increase DMT-1
-> absorb more iron - increase ferroportin
-> excrete more iron out of intestinal cells - increase transferrin receptor
-> bind to more iron to transport more iron
definition of lymphoma
malignancies of lymphoid system that manifests outside the bone marrow
malignancies of lymphoid system
= abnormal growth and proliferation of lymphocytes
and their differences in terms of characteristics
types of lymphomas
- aggressive lymphomas
fast
BUT localised
and responsive and curable w/ aggressive therapy - indolent lymphomas
slow
BUT widespread
and mostly incurable
characteristics of Hodgkin lymphoma
Reed-Sternberg cells
- large
- “owl’s eyes”
Which of the following is the most common type of B-cell lymphoma?
A) Burkitt Lymphoma
B) Mantle Cell Lymphoma
C) Diffuse Large B-Cell Lymphoma (DLBCL)
D) Follicular Lymphoma
C) Diffuse Large B-Cell Lymphoma (DLBCL)
Which B-cell lymphoma is associated with the “starry sky” appearance on histology and is linked to Epstein-Barr Virus (EBV)?
A) Diffuse Large B-Cell Lymphoma
B) Burkitt Lymphoma
C) Follicular Lymphoma
D) Mantle Cell Lymphoma
B) Burkitt Lymphoma
t(8;14) transolcation
-> C-MYC now under control of lgH promotor
-> upregulated expression of C-MYC
(transcription factor regulating cell proliferation and growth)
=> uncontrolled cell proliferation
“can rmb as number 8 in front which looks like infinity sign ∞
= translocation result in cell multiplying constantly
=> uncontrolled cell proliferation”
t(8;14) bcos burkitt has 7 letters so 7+1=8, 14 always at the back
all 3 (burkitt, mantle cell and follicular) lymphoma are due to
translocation of gene segment
-> gene under control of lgH promotor
=> overexpression
Which lymphoma is associated with overexpression of BCL-2, preventing apoptosis?
A) Diffuse Large B-Cell Lymphoma
B) Burkitt Lymphoma
C) Mantle Cell Lymphoma
D) Follicular Lymphoma
D) Follicular Lymphoma
t(14;18) translocation
-> BCL-2 now under control of lgH promotor
-> upregulated expression of BCL-2
(transcription factor regulating apoptosis)
=> blockade of apoptosis and cell survival
“can rmb as number 4 in front
= translocation result in cell 不能死
=> prevents apoptosis”
only one where cannot count letters + 14 at the front instead of back
Which B-cell lymphoma is considered indolent and slow-growing compared to the others?
A) Burkitt Lymphoma
B) Diffuse Large B-Cell Lymphoma
C) Mantle Cell Lymphoma
D) Follicular Lymphoma
D) Follicular Lymphoma
what are the ferritin levels like in haemolytic anaemia?
haemolytic anaemia is a form of normocytic anaemia
High
* increased iron release from hemolyzed RBCs
* also present as acute phase reactant
<- haemolysis can trigger inflammation
type of anaemia
what is jaundice commonly associated with
haemolytic anaemia
results in increased release of Hb from destroyed RBCs
→ increased conversion of Hb to unconjugated bilirubin
→ elevated levels of unconjugated bilirubin,
exceeds liver processing capacity
(i.e. rate at which liver conjugates bilirubin)
⇒ yellow unconjugated bilirubin deposit in skin and other tissues,
causing the characteristic yellowing seen in jaundice
also seen in other conditions where there is elevated levels of unconjugated bilirubin
(e.g. megaloblastic anaemia where there is premature desturction of RBCs)
blood smear finding for megaloblastic anaemia
hypersegmented neutrophil
due to impaired DNA synthesis
→ nucleus does not divide and segment properly
⇒ nucleus ends up with many lobes (> 6)
usually 3-5 lobes
how can G6PD or PK deficiency lead to pre-hepatic jaundice
- G6PD is crucial for production of NADPH
→ helps protect RBCs from oxidative stress - PK is essential for glycolysis
→ by which RBCs generate energy - Lack of either
→ RBCs are more easily destroyed
(i.e. haemolysis)
⇒ lead to pre-hepatic jaundice
mechanism of neonatal jaundice
due to liver immaturity
→ lower levels of UDP-glucuronosyltransferase
(enzyme responsible for conjuation)
→ production > conjugation for bilirubin
→ buildup of unconjugated bilirubin
⇒ jaundice
what does positive Direct Coombs Test indicate
jaundice (or any other disease) has an immune cause
what should be given for immediate restorance of hemostatic competence?
e.g. during excessive anticoagulation due to warfarin overdose
fresh frozen plasma
bcos it contains ready-to-use clotting factors
treatment for mild to moderate vWD
desmopressin
1st-line treatment as it
* stimulates vWF release from Weibel-Palade bodies
* increases Factor VIII levels
can also be used prophylactically
treatment for haemophilia if patient develops inhibitors against clotting factor replacement
i.e. recombinant factors
how it works: body produce antibodies against the clotting factor replacement
-> preventing replacement factor from working
Activated Prothrombin Complex Concentrates (APCC)
which contain a mix of several clotting factors
which are already partially activated
→ bypass need for factor that is deficient
compared to fresh frozen plasma which also has many clotting factors,
but are all inactivated and thus may require activation by the inhibited factors
⇒ will not work
An 8-year-old boy was found to have a swollen right knee. Investigations revealed blood in the right knee. While the bleeding time and aPTT was prolonged, PT was normal. The levels of factors VIII and IX were also normal. Which is MOST LIKELY to be true?
A. Both coagulation pathways are expected to be normal
B. Factor V is deficient
C. Factor VIII function is impaired
D. Serum calcium is expected to be low
E. Prothrombin is low
C. Factor VIII function is impaired
- bleeding time and aPTT was prolonged
→ indicative of haemophilia
- bleeding time and aPTT was prolonged
- The levels of factors VIII and IX were also normal
→ seems to not be haemophilia
⇒ haemophilia where there are normal levels BUT abnormal function
Which is the MOST LIKELY potential side effect of a massive blood transfusion?
A. Hyperthermia
B. Raised conjugated bilirubin level in blood
C. Reduced total body iron stores
D. Low ionised calcium level in blood
E. Increased thrombosis
D. Low ionised calcium level in blood
as blood that is transfused likely has citrate
(acts as calcium chelator to prevent blood from coagulating before transfusion)
-> liver may be unable to metabolise citrate in transfused blood quickly
-> excess chelate binds to calcium ions
=> lower levels of calcium ions in blood
most common thymic pathology in children and adult respectively?
A) thymoma
B) non-hodgkin lymphoma
C) germ cell tumours
D) hodgkin lymphoma
thymic pathology = conditions affecting thymus
- children: non-hodgkin lymphoma
- adults: thymoma
petechiae, purpura, ecchymosis
difference in size of haemorrhages
petechiae: less than 1/2 cm
purpura: up to 1 cm
ecchymosis: 2-3 cm
what type of haemorrhage usually present in coagulation factor deficiency
ecchymosis
definition of oedema
excessive extravascular accumulation of fluid
in interstitial tissues and body cavities
presence of (…) is used to diagnose amniotic fluid embolism
when amniotic fluid enters maternal circulation via tears in placenta during childbirth/parturition or abortions
=> occlusion of pulmonary arteries
presence of foetal squames
(i.e. foetal squamous cells)
in mother’s blood
