1
Q
What is the blood volume of RBCs?
A
40-50%
1
Q
What is the average life of RBCs?
A
120 days - removed by the spleen
2
Q
What controls the production of RBCs?
A
Erythropoietin (kidney)
3
Q
What do RBCs contain?
A
Haemoglobin
- 4 globin chains, each with heme group
4
Q
Types of haemoglobin?
A
- HbA: 2 alpha, 2 beta chains (adult)
- HbF: 2 alpha, 2 gamma chains (fetus)
- In fetus/newborn (HbF) 2 gamma subunits in place of the
beta subunits.
5
Q
What does lack of iron do in RBCs?
A
Reduces the amount of Hb in blood cells
6
Q
What is anemia?
A
Reduction in the mass of circulating RBCs
- Results in reduction of oxygen carrying capacity of blood.
7
Q
What does blood analysis show in anaemia?
A
- Low red blood cell count
- Low haemoglobin
- Low haematocrit count
8
Q
What are the mechanisms of anaemia?
A
- Decreased red cell production
- Increased red cell destruction
9
Q
What are examples of anaemia due to decreased red cell production?
A
- Iron deficiency Anaemia, most common
- Vit B12 deficiencies Anaemia
- Folate deficiencies Anaemia
- Aplastic Anaemia
- Anaemia of chronic disorders
10
Q
What are examples of anaemia due to increased red cell destruction?
A
- Haemorrhage
- Haemolytic Anaemias
11
Q
Clinical features of anaemia?
A
12
Q
What is iron deficiency anaemia?
A
occurs when the body does not have enough iron to produce adequate haemoglobin
13
Q
What are the causes of iron deficiency anaemia?
A
- Inadequate dietary intake
- Poor iron absorption
- Blood loss
14
Q
Iron deficiency Anaemia treatments
A
- Rectify underlaying cause
- Sufficient iron intake in diet
- Oral iron supplement i.e ferrous sulphate
- Parenteral I.M ( I.V. avoided as can cause anaphylaxis)
- Blood transfusion if severe
15
Q
(Iron Cycle) Where in the body is dietary iron primarily absorbed?
A
In the small intestine.
16
Q
(Iron Cycle) What forms of food are sources of dietary iron?
A
Meat and vegetables.
17
Q
(Iron Transport Mechanism) Which protein binds iron in the blood plasma for transport?
A
Transferrin.
18
Q
(Iron Storage Mechanism) In which organ is most iron stored, and in complex with which protein?
A
Stored in the liver, complexed with ferritin.
19
Q
(Iron Storage Indicator) Which protein leaks from tissues into the bloodstream and serves as a measure of body iron stores?
A
Ferritin (measured as serum ferritin).
20
Q
(Iron Deficiency Indicator) What does a low serum ferritin level indicate?
A
Depleted iron stores, suggesting iron deficiency.
21
Q
(Iron Deficiency Anaemia Morphology) What type of anaemia morphology is characteristic of iron deficiency?
A
Hypochromic microcytic anaemia.
22
Q
(Iron Deficiency Anaemia RBC Appearance) How do red blood cells appear in iron deficiency anaemia?
A
Small (microcytic) and pale (hypochromic).
23
Q
(Iron Deficiency Anaemia Lab Findings) What happens to total serum iron (SI) levels in iron deficiency anaemia?
A
They decrease (low total serum iron).
24
(Iron Deficiency Anaemia Lab Findings) What happens to total iron-binding capacity (TIBC) in iron deficiency anaemia?
It increases (due to unsaturated transferrin).
25
(Iron Deficiency Anaemia Specific Marker) What is considered one of the most specific lab indicators of iron deficiency?
Decreased serum ferritin.
26
Causes of B12 deficiecny?
- Autoimmune
- Malabsorption
- Inadequate diet
27
What type of vitamin is Vitamin B12, and from which dietary sources is it derived?
Vitamin B12 is a water-soluble vitamin obtained from animal products such as red meat, dairy, and eggs.
28
Which gastric cells produce intrinsic factor required for B12 absorption?
Parietal cells of the stomach.
29
In which part of the gastrointestinal tract is Vitamin B12 absorbed?
The terminal ileum.
30
Which biochemical processes require Vitamin B12 as a cofactor?
DNA synthesis, fatty acid synthesis, and myelin synthesis.
31
Why can Vitamin B12 deficiency cause both haematologic and neurologic symptoms?
Because B12 is necessary for DNA synthesis (affecting red blood cell production) and myelin formation (affecting the nervous system).
32
After absorption, which protein binds Vitamin B12 for transport in the bloodstream?
Transcobalamin II.
33
Which organs and tissues store Vitamin B12 in the body?
The liver, bone marrow, and other tissues.
34
What autoimmune condition causes B12 deficiency by targeting intrinsic factor?
Pernicious anaemia.
35
How do intrinsic factor antibodies in pernicious anaemia lead to B12 malabsorption?
They inhibit intrinsic factor’s function, preventing B12 absorption in the terminal ileum.
36
Name three gastrointestinal conditions or surgeries that can lead to B12 malabsorption.
Gastric bypass surgery, surgical resection due to Crohn’s disease, and celiac disease.
37
Which intestinal parasite infection can cause B12 deficiency?
Diphyllobothrium latum (fish tapeworm).
38
What dietary habit can lead to B12 deficiency over time?
A long-term vegan diet (no animal products).
39
B12 Deficiency Clinical Presentation
* Fatigue and pale
* Jaundice may also be a presenting symptom
* Glossitis (inflamed and swollen tongue)
* Diarrhea
* Peripheral neuropathy (numbness and tingling in extremities)
* Headaches
* Neuropsychiatric disturbances
40
B12 deficiency diagnosis
* History and physical exam
* Reduced level Hb, haematocrit or RBC
* Blood smear: macrocytic anaemia, hypersegmented neutrophils
* Reduced Serum B12
41
How to treat B12 deficiency?
- Treat underlying condition
- Repletion with B12
- Dietary changes
42
What is folate deficiency anaemia?
Where the body has insufficient folate (vitamin B9)
43
What is folate important for?
DNA synthesis, RBC formation and proper cell division
44
Which metabolic reaction involving homocysteine is impaired in Vitamin B12 deficiency?
The conversion of homocysteine to methionine.
45
In B12 deficiency, what happens to methyl-THF and THF during the folate cycle?
Methyl-THF cannot be converted to THF, leading to a functional folate deficiency.
46
How does impaired THF regeneration affect DNA synthesis?
It prevents proper pyrimidine base formation, resulting in reduced DNA synthesis.
47
What type of anaemia results from reduced DNA synthesis in B12 deficiency?
Megaloblastic anaemia (characterized by large RBCs).
48
Besides red blood cells, which other rapidly dividing cell line is affected in B12 deficiency?
Neutrophils (leading to abnormal nuclear segmentation).
49
What distinctive white blood cell finding is seen in B12 deficiency?
Hypersegmented neutrophils.
50
Which enzyme requires Vitamin B12 to convert methylmalonyl-CoA to succinyl-CoA?
Methylmalonyl-CoA mutase.
51
Which compound accumulates due to impaired methylmalonyl-CoA metabolism in B12 deficiency?
Methylmalonic acid (MMA).
52
Which two metabolites are elevated in Vitamin B12 deficiency?
Homocysteine and methylmalonic acid (MMA).
53
How do elevated MMA and homocysteine levels contribute to neurological symptoms?
They cause myelin damage, leading to neurological deficits.
54
What causes folate deficiency?
- Inadequate intake
- Drugs that antagonize folate utilization
- Elevated pH
- Alcohol
- Malabsorption
- Increased demand
55
Clinical presentation of folate deficiency?
Most of these symptoms overlap with symptoms of vitamin B-12 deficiency except for the classical neurological features of B12 deficiency
56
What are the treatment options of folate defiency anaemia?
* Treating underlying causes
* Oral Folic Acid
* Dietary changes
57
In what chemical form is most serum folate present?
As inactive 5-methyltetrahydrofolate (5-methyl THFA).
58
How is 5-methyl THFA converted into the biologically active form inside cells?
It undergoes demethylation to form tetrahydrofolate (THFA).
59
Which form of folate is required for purine synthesis?
5,10-methyltetrahydrofolate (5,10-methyl THFA).
60
How does folate deficiency impair cell division?
By reducing purine and thymidine synthesis, which disrupts DNA synthesis and slows mitosis.
61
What accumulates in cells as a result of impaired folate metabolism?
Toxic metabolites due to disrupted one-carbon metabolism.
62
How does folate deficiency affect methylation reactions in the body?
It impairs methylation reactions required for the regulation of gene expression and other metabolic processes.
63
Which type of cells are most affected by folate deficiency?
Rapidly dividing cells, especially blood cells.
64
What type of anaemia results from folate deficiency?
Megaloblastic anaemia due to impaired DNA synthesis in red cell precursors.
65
What is aplastic anaemia?
Failure of production of stem cells in bone marrow
- Important hallmark: reduced numbers of all blood cell
types RBC, WBC and thrombocytes
66
Aetiology of Aplastic Anaemia?
* Hereditary i.e Fanconi Anaemia
* Radiation
* Chemotherapy
* Drugs: Gold, NSAIDs
* Benzene
* Viruses i.e hepatitis
67
What are the two pathophysiology of aplastic anaemia?
1. Extrinsic immune-mediated
suppression of hematopoietic
stem cells
2. Intrinsic abnormality of
marrow progenitor
68
What is the mechanism of extrinsic immune-mediated suppression of hematopoietic stem cells?
Damaged hematopoietic stem cells activate self-reactive T-helper 1 (Th1) cells, which release cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor (TNF). These cytokines trigger a cytotoxic cascade that kills and suppresses other hematopoietic stem cells, leading to bone marrow failure.
69
What is the mechanism behind intrinsic abnormality of marrow progenitor cells?
Hematopoietic stem cells with inherent defects lose their ability to differentiate and proliferate. Partial defects in telomeres cause premature stem cell exhaustion, leading to bone marrow aplasia.
70
Aplastic Anaemia Clinical Presentation
* Presents at any age with equal distribution among gender and
race
* Signs of Anaemia
* Progressive weakness
* Pallor
* Shortness of breath
* Reduced neutrophil count (Neutropenia)
* Thrombocytopenia, mucosal bleeding
* Frequent and persistent minor infections, or sudden onset
febrile illness
71
Aplastic Anaemia Diagnosis
* Complete blood count (CBC): Shows pancytopenia (low levels of red blood cells, white blood cells, and platelets)
* Bone marrow biopsy (essential): hypocellularity
* Tests for underlying causes e.g viral infections
72
Aplastic Anaemia Treatment
* Directed at the underlying cause
* Avoid trigger factors
* Immunosuppressive therapy
* Anti-thymocyte globulin plus antibiotics
* Bone marrow or peripheral blood transplant
73
What is haemolytic anaemia?
A condition in which red blood cells (RBCs) are destroyed faster than they can be produced by the bone marrow
74
What are the causes of haemolytic anaemia?
Due to intrinsic causes:
* Hereditary spherocytosis
* Sickle cell anaemia
* Thalassemia
Extrinsic abnormalities (caused by factors introduced from outside the RBC):
* Autoimmune haemolytic anaemia
* Infections
75
Immune haemolytic Anaemia
* Is an example of extrinsic cause
* Antibodies to RBCs
Occurs in:
* Idiopathic
* Drug reaction to Methyldopa, Penicillin
* Diseases such as mycoplasma,
mononucleosis, lymphomas
* Transfusion reactions: ABO blood groups
* Haemolytic disease of newborn: Rhesus, ABO systems
76
Sickle cell Anaemia - Haemolytic anaemia examples
* Autosomal recessive inheritance
* HbA à HbS due to amino acid
substitution in beta chain
* Characterised by crescent RBC
morphology àimpaired O2 carrying capacity
77
Thalassemia - Haemolytic anaemia examples
* Autosomal recessive inheritance
* Defective synthesis of a or b chains
* Abnormal Hb aggregates -increased RBC destruction in marrow and spleen
* Accompanied by bone deformity and spleen enlargement
* hypochromic, microcytic RBCs with various shapes
* The presence of Target cell
78
Haemolytic Anaemias Clinical Presentations
Signs and symptoms associated with Anaemia e.g shortness of breath, weakness, fatigue, arrhythmias such as
tachycardia
* Jaundice
* Haematuria
79
Haemolytic Anaemia Diagnosis
History and Physical examination
Lab tests:
* Hb, RBC or haematocrit (Low)
* Blood smear is essential
* Serum bilirubin: Elevated, particularly unconjugated bilirubin
* Lactate dehydrogenase (LDH): increase in haemolytic Anaemia
* For immune mediated: Direct Coombs test positive in autoimmune haemolytic anaemia, indicating the presence of antibodies against RBCs.
80
Haemolytic Anaemia management
* Specific treatment toward the cause
* Blood transfusion
* Prophylactic anticoagulation
For autoimmune haemolytic Anaemias:
* Splenectomy, in cases where the spleen is the site of significant RBC destruction
* Steroids for autoimmune haemolytic anaemia
* Plasmapheresis: in severe cases of autoimmune haemolytic anaemia to remove antibodies from the blood.
81
What is haemostasis?
the process which causes bleeding to stop
- Delicate balance between the
actions of platelets, endothelial
cells and coagulation factors
82
What are the 3 key areas of coagulation?
1. Endothelium
2. Platelets
3. Clottin Factors
83
What are the stages of normal haemostasis?
1. Vessel spasm
2. Platelet plug formation
3. Blood coagulation cascade
4. Clot retraction
5. Clot lysis
84
What is thrombosis?
Blood clot within blood vessels limiting the natural flow of blood
85
86
Three major factors involved in thrombus formation
1. Stasis
2. Hypercoagulability
3. Vessel wall injury
87
Hypercoagulability
Increased clotting potential of the blood = blood clots more than normal (inappropriate
clotting)
88
What can hypercoagulability be due to?
* Increased platelet function
* Increased platelet numbers (thrombocytosis)
* Increased activity of the clotting system
89
Causes of hypercoagulability?
- Increased platelet function
- Increased platelet numbers
- Increased clotting activity
90
What are the causes of venous stasis?
- Bed rest
- Immobility
- Spinal cord injury
- Acute myocardial infarction
- Shock
- Venous obstruction
91
Causes of vascular trauma?
- Indwelling venous catheters
- Surgery
- Massive trauma or infection
- Fractured hip
- Orthopaedic surgery
92
Fate of Thrombi: What happens after formation?
1. Propagation = enlargement of the thrombus
2. Organisation = fibrous repair
3. Resolution = dissolution of the clot
4. Embolisation= detachment
and movement
93
What veins are painful?
Superficial veins
94
What is embolus?
Thrombus breaks off and travels in the blood stream.
95
What is deep vein thrombosis?
Development of a blood clot in a deep vein
96
Where does DVT most commonly occur?
Legs
97
What are the risk factors of DVT?
- Stasis = decrease BF
- Increased coagulability of blood
- Blood vessel injury
98
What are the signs and symptoms of DVT?
- Swelling
- Tenderness
- Pain (may be radiating)
- Warmth
- Redness
99
How do emboli travel to the lungs?
From deep vein of leg:
- Inferior vena cava
- Right atrium of heart
- Right ventricle of heart
- Pulmonary trunk
- Pulmonary artery
- Embolus lodges when it is to big to pass any further
100
Symptoms of pulmonary emboli?
- Chest pain
- Palpitations
- Shortness of breath
- Coughing
- Shock, sudden death
101
What is the treatment of DVT?
- Body positions
- Medications
- Surgical
102
What body positions treatm DVT?
- Elevation of legs to present stasis
- Maintain extension (avoid flexion)
- Heat
- Compression stockings
103
What medications treat DVT?
- ANticoagulants therapy (heparin and warfarin)
- Thrombolytic therapy
104
What surgical treatments of DVT?
- Thrombectomy
- Insertion of inferior vena cava
105
What is superficial vein thrombosis?
When clots form in superficial veins
106
What can SVT lead to in adjacent skin and fat?
Inflammation
- Tender lumb under skin
- Pink skin overlying thrombus
107
What is the most common cause of SVT?
Varicose veins
- Enlarged and result in slow BF
108
What is arterial thombosis?
Blood clot blocking an artery
109
what is the difference between vein and artery thrombosis?
Venous thrombosis is when the blood clot blocks a vein. Arterial thrombosis is when the blood clot blocks an artery.
110
What is thrombocytopenia?
decrease in platelet number
111
What can decrease in platelet number be due to?
* Decreased platelet production
* Increased sequestration of platelets in the spleen
* Decreased platelet survival time
112
What are the causes of thrombocytopaenia?
* Leukaemia
* Chemotherapy/ radiotherapy
* Aplastic anaemia: Reduced/no production of
megakaryocyte precursor cells in bone marrow
* Drug-induced Thrombocytopaenia
113
What is Von Willebrand Disease?
* Most common hereditary bleeding disorder
* Reduced levels of functional von Willebrand Factor (vWF)
114
What is type 1 Von Willebrand Disease?
Low levels of VWF, may have slightly low factor VIII levels
* Autosomal dominant
115
What is type 2 Von Willebrand Disease?
Levels of VWF may be normal, but it does not work properly
* Qualitative defect in vWF
* Several subtypes
116
What is type 3 Von Willebrand Disease?
Absent or extremely low levels of VWF, factor VIII levels will also be very low
* Usually caused by deletions or frameshift mutations involving both alleles, resulting in little to no vWF synthesis = reduced F VIII = often severe bleeding
117
What are the symptoms of von Willebrand Disease
- Easy bruisin
- Excessive menstrual flow
- nose bleeds
- mouth bleeds
118
What is Haemophilia A?
X-linked recessive disorder - primarily affects males –(only have one X chromosome).
118
What is the management of von Willebrand Disease?
- Desmopressin
- Infusions of plasma concentrated containing factor VIII and VWF
- Antifibrinolytic agents
119
What factor is haemophilia A linked to?
Mutations of Factor VIII gene (essential for blood clotting)
120
What are the symptoms of Haemophilia A?
- Bleeding in soft tissues, GIT, joints
- Spontaneous joint bleeding when child starts walking
- Prone to repeated bleeding episodes
- Bleeding causes inflammation of joint synovium
121
What is Haemophilia B?
* is a similar disorder involving mutation of the factor IX gene
* factors VIII and IX function together to activate factor X.
* X-linked recessive
122
Treatment of Haemophilia?
- Prevention of trauma
- Avoid: Aspirin and NSAIDs that affect platelet function
- Factor VIII replcement therapy for A and Factor IX for B
123
What is Disseminated Intravascular Coagulation (DIC)
Not primary disease but acquire coagulopathy
- Widespread coagulation and bleeding within the vascular compartment causing organ damage
124
What can activate DIC?
Events that cause tissue injury or endothelial cell injury
125
What conditions are associated with DIC?
- Obstetric complications
- Cancers
- Infections
- Shock
- Trauma/surgery
- Haemoatologic conditions
126
What two mechanisms trigger DIC?
- RElease of tissue factor or other procoagulants into the circulation
- Widespread injury of endothelial cells
127
What is the basic pathophysiology of Disseminated Intravascular Coagulation (DIC)?
DIC is an imbalance between clotting and bleeding.
Overactivation of the coagulation cascade (mainly the extrinsic pathway) → excessive thrombin and fibrin → widespread microthrombi.
This uses up platelets and clotting factors, leading to bleeding.
At the same time, fibrinolysis breaks down clots → further haemorrhage risk.
Micro- and macrovascular clots reduce blood flow → tissue ischemia → can lead to Multi-Organ Dysfunction Syndrome (MODS).
128
What are the signs and symptoms of DIC?
- Onsent may be fulminant or insidious
- Acute DIC = obstetric complications or major trauma
- Chronic DIC = cancer patients, thrombotic complications
129
What is the treatment for DIC?
* Management of primary disease is the main goal
* Replacing clotting components
* Preventing further activation of clotting mechanisms
* Managing complications such as bleeding or thrombosis
130
What is laukemia?
Heterogeneous group of blood cancer that arise from the dysfunctional and uncontrolled proliferation of WBCs
131
What is leukemia classfied as?
* Acute or chronic
* Myelocytic or lymphocytic
132
What are the Predominant subtypes of leukemia?
Myeloid lineage
* Acute Myeloid Leukemia (AML)
* Chronic Myeloid Leukemia (CML)
Lymphoid lineage
* Acute Lymphoblastic leukemia (ALL)
* Chronic Lymphocytic leukemia (CLL)
133
Acute Leukemia:
* Is characterized by greater than 20% blasts (immature cells) in
the peripheral blood smear or on bone marrow
* leading to a more rapid onset of symptoms
134
Chronic leukemia:
* has less than 20% blasts
* relatively chronic onset of symptoms
135
What is the most common feature of acute leukemia?
Fever, lethargy and bleeding
136
What symptoms may adults have that indicated acute leukemia?
Prominent anaemia-related symptoms
- Shortness of breath
Thrombpcytopenia symptoms:
- Excessive bruising
- HEavy menstrual cycles
137
Chronic leukemia symptoms?
Usually asymptomatic at time of diagnosis
- Hepatosplenomegaly and lymphadenopathy can
be appreciated in some cases while bleeding and
bruising are less common
138
What characterises Acute Myeloid Leukemia (AML)?
> 20% myeloid blasts
139
What age group is Acute Myeloid Leukemia (AML) common in?
Adults
140
What is the most aggressive cancer?
Acute Myeloid Leukemia (AML)
141
What is the basic pathophysiology of Acute Myeloid Leukemia (AML)?
Chromosomal changes (translocations, rearrangements, or losses/gains) cause mutations and abnormal myeloblast production.
A key translocation is t(15;17) → fusion of PML and RARA genes.
This forms acute promyelocytic leukemia (APL), a subtype of AML.
APL is linked with DIC features and requires urgent treatment.
142
What are the causes of Chronic Myeloid Leukemia (CML)?
Chromosomal abnormalities in
hematopoietic stem cells that are precursors to leukocytes
- Leads to monoclonal pop. of dysfunction granulocytes
143
What is the basic pathophysiology of Chronic Myeloid Leukemia (CML)?
Caused by a reciprocal translocation between chromosome 9 (ABL1) and chromosome 22 (BCR).
This forms the BCR-ABL fusion gene on chromosome 22, known as the Philadelphia chromosome.
The fusion gene causes uncontrolled cell growth and leukemia development.
144
What is Acute Lymphoblastic Leukemia (ALL)?
Blastic transformation of B and T cells
145
What is the most common leukemia in paediatrics?
Acute Lymphoblastic Leukemia (ALL)
146
What is Chronic Lymphocytic Leukemia (CLL)?
From proliferation of monoclonal lymphoid cells
147
What age does Chronic Lymphocytic Leukemia (CLL) most commonly occur in?
60-70
148
What is the basic pathophysiology of Chronic Lymphocytic Leukemia (CLL)?
Begins with a mutation in early B-cell development that increases cell growth and survival.
Immune stimulation (with or without T cells) causes clonal B-cell proliferation.
Over time, genetic changes and interactions with the microenvironment promote further clonal expansion, leading to leukemia.
149
What is the diagnosis of leukemia?
* Complete blood count (CBC)
* Peripheral blood and a bone marrow smear
* More detailed analyses with flow cytometry, cytogenetic, testing –to distinguish between subtypes
150
What is the treatment/management of leukemia?
Varies depending on subtype and patient:
- Non-chemotherapy
- Chemotherapy
- Radiation therapy
- Targeted therapy
- Stem cell transplant
Systemic Pathology
flashcards
Decks in class (12)
# Cards
