Facial nerve palsy can result in inability to close the eye due to paralysis of the orbicularis oculi muscle. Elevation of the eyelid in eye opening is a function of the levator palpebrae superioris muscle and the superior tarsal muscle, innervated by the oculomotor nerve and the sympathetic chain respectively.

Abducens nerve palsies result in a convergent squint at rest (eye turned inwards) with inability to abduct the eye because of unopposed action of the rectus medialis. The patient complains of horizontal diplopia when looking towards the affected side. With complete paralysis, the eye cannot abduct past the midline.

Neutrophils are the most numerous peripheral blood leukocytes, accounting for 50-70 percent of all circulating white cells. Neutrophils have a compact nucleus with two to five lobes and a pale cytoplasm with an irregular shape containing numerous fine pink-blue or grey-blue granules. The granules are classified as primary, which emerges during the promyelocyte stage, and secondary, which develop at the myelocyte stage and predominate in the mature nucleus.

The lifespan of neutrophils in the blood is only 6 – 10 hours. In response to tissue damage, cytokines and complement proteins, neutrophils migrate from the bloodstream to the site of insult within minutes, where they destroy pathogens by phagocytosis.

Acute lymphoblastic leukaemia (ALL) is caused by an accumulation of lymphoblasts in the bone marrow and is the most common malignancy of childhood. The incidence of ALL is highest at 3 – 7 years, with 75% of cases occurring before the age of 6. 85% of cases are of B-cell lineage. Haematological investigations reveal a normochromic normocytic anaemia with thrombocytopenia in most cases. There is great variation in the chance of individual patients achieving a long-term cure based on a number of biological variables. Approximately 25% of children relapse after first-line therapy and need further treatment but overall 90% of children can expect to be cured. The cure rate in adults drops significantly to less than 5% over the age of 70 years.

Once muscle tissue is damaged, there will be healing via diffuse formation of fibrous tissue, especially due to the widespread ischemia.

Callus formation takes place in the healing of bone, not muscle.

Organised scar formation occurs when a lacerated wound is approximated by sutures so that primary intention wound healing can occur.

Liquefaction degeneration occurs following ischemia in the brain.

Volkmann’s ischemic contracture may occur, but it is not the primary type of healing that will take place but rather the effect of the fibrous scar formation.

Anti-nuclear antibodies are auto-antibodies directed against a variety of nuclear antigens. There are different staining patterns and each pattern is suggestive of a different disorder.

Speckled staining is suggestive of mixed connective tissue disease.

Nucleolar staining is suggestive of scleroderma, while homogenous staining is suggestive of lupus.

Anti-double stranded DNA is suggestive of SLE while anti-histone antibodies are suggestive of drug-induced lupus.

ELISA testing is cheaper but not the most accurate means of testing for ANAs. Indirect immunofluorescence testing is the most accurate.

The presence of ANAs in rheumatoid arthritis is suggestive of Felty’s syndrome. Felty’s syndrome is characterized by a combination of rheumatoid arthritis, splenomegaly and neutropenia.

CLL (chronic lymphocytic leukaemia) is the most common type of chronic lymphoid leukaemia, with a peak incidence between the ages of 60 and 80. It is the most common type of leukaemia in Europe and the United States, but it is less common elsewhere.

The CLL tumour cell is a mature B-cell with low immunoglobulin surface expression (IgM or IgD). The average age at diagnosis is 72 years, with only 15% of cases occurring before the age of 50.

The male-to-female ratio is about 2:1. Over 80% of cases are identified by the results of a routine blood test, which is usually performed for another reason.

Lymphocytic anaemia, thrombocytopenia, and normochromic normocytic anaemia are common laboratory findings. Aspiration of bone marrow reveals up to 95% lymphocytic replacement of normal marrow elements.

Histamine increases vascular permeability in the acute inflammatory response.

Histamine causes vasodilation.

It is released from Mast cells and basophils, eosinophils and platelets.

Mast cells and basophils are its primary source

Nitric oxide (not histamine) is a major factor in endotoxic shock

IgA is the major Ig in secretions, particularly from the gastrointestinal tract (but also in saliva, tears, sweat and breast milk).
IgE is important for mast cell degranulation in allergic and antiparasitic response. In the allergic response, the plasma cell produces IgE-antibodies, which, like antibodies of other immunoglobulin isotypes, are capable of binding a specific allergen via its Fab portion.
IgG is the most abundant in plasma (comprising 80% of normal serum immunoglobulin) and the main circulatory Ig for the secondary immune response.

B-cells (20% of lymphocytes) mature in the bone marrow and circulate in the peripheral blood until they undergo recognition of antigen. B-cell immunoglobulin molecules synthesised in the cell are exported and bound to the surface membrane to become the B-cell receptor (BCR) which can recognise and bind to a specific antigen (either free or presented by APCs). The BCR is also important for antigen internalisation, processing and presentation to T helper cells. Most antibody responses require help from antigen-specific T helper cells (although some antigens such as polysaccharide can lead to T-cell independent B-cell antibody production). When the B-cell is activated, the receptor itself is secreted as free soluble immunoglobulin and the B-cell matures into a memory B-cell or a plasma cell (a B-cell in its high-rate immunoglobulin secreting state). Plasma cells are non-motile and are found predominantly in the bone marrow or spleen. Most plasma cells are short-lived (1 – 2 weeks) but some may survive much longer. A proportion of B-cells persist as memory cells, whose increased number and rapid response underlies the augmented secondary response of the adaptive immune system.

The history of nosebleeds and fatigue, and gingival hyperplasia presents a typical picture of acute myeloid leukaemia. Leukemic infiltrates within the gingiva cause hypertrophy and distinguish this condition from other types of leukaemia. The fatigue is secondary to anaemia, while the nosebleeds are caused by thrombocytopenia secondary to leukemic infiltration of bone marrow. Patients may also report frequent infections secondary to neutropenia and hepatosplenomegaly.

Neutrophils are the most abundant peripheral blood leucocyte, comprising about 50 – 70% of circulating white cells. Neutrophils have a characteristic dense nucleus consisting of between two and five lobes, and a pale cytoplasm with an irregular outline containing many fine pink-blue or grey-blue granules. The granules are divided into primary, which appear at the promyelocyte stage, and secondary, which appear at the myelocyte stage and predominate in the mature nucleus. Both types of granule are lysosomal in origin; the primary contains myeloperoxidase and other acid hydrolases; the secondary contains lactoferrin, lysozyme and other enzymes. The lifespan of neutrophils in the blood is only 6 – 10 hours. In response to tissue damage, cytokines and complement proteins, neutrophils migrate from the bloodstream to the site of insult within minutes, where they destroy pathogens by phagocytosis.

The presence of Reed-Sternberg cells is pathognomonic for Hodgkin’s Lymphoma, which is a disease-causing neoplastic transformation of lymphocytes. There is a bimodal age distribution with peaks in the 20s and 60s. Patients typically present with enlarged, rubbery, non-tender lymph nodes. Symptoms such as fever, night sweats and weight loss may be present.

Pain after alcohol consumption is a pathognomonic sign of Hodgkin’s lymphoma, it is, however, not a ‘B’ symptom. It is rare though, only occurring in 2-3% of patients with Hodgkin’s lymphoma.
The Ann Arbour clinical staging is as follows:
Stage I: one involved lymph node group
Stage II two involved lymph node groups on one side of the diaphragm
Stage III: lymph node groups involved on both sides of the diaphragm
Stage IV: Involvement of extra-nodal tissues, such as the liver or bone marrow
Diagnosis is made by lymph node biopsy, which should be taken from a sufficiently large specimen or excisional biopsy, as opposed to a fine needle biopsy.

Multiple myeloma most commonly presents with bone pain, especially in the back and ribs.

In non-Hodgkin’s lymphoma, Reed-Sternberg cells are not present.

Acute lymphoblastic leukaemia will present with features of anaemia, thrombocytopenia and leukopenia.

The most common symptoms of chronic lymphocytic leukaemia are fatigue, night sweats and low-grade fever.

C-reactive protein(CRP) is synthesized in the liver in response to increased interleukin-6 (IL-6) secretion by macrophages and T-cells.
Some conditions that cause CRP levels to a rise include: bacterial infection, fungal infection, severe trauma, autoimmune disease, Organ tissue necrosis, malignancy and surgery.

It is useful in the clinical setting as a marker of inflammatory activity and can be used to monitor infections.

CRP levels start to rise 4-6 hours after an inflammatory trigger and reaches peak levels at 36-50 hours.

In the absence of a disease process, the normal plasma concentration is less than 5 mg/l.

CRP is useful for monitoring inflammatory conditions (e.g. rheumatoid arthritis and malignancy), can be used as a prognostic marker in acute pancreatitis, and serial measurement can be used to recognize the onset of nosocomial infections in the intensive care settling.

IgA is the predominant antibody class in secretions and tremendous quantities are secreted into various body spaces and onto mucosal surfaces (the gut lumen, the pharynx and sinuses, the larger airways, although not the alveoli).
Because of its size, the majority of IgM is found in the circulation.

Along with IgM, IgD is predominant among the surface receptors of mature B cells, where it plays a key role in B cells activation.

IgE has the lowest concentration in normal human serum. It plays a prominent role in immune responses to helminth parasites, and in allergic reactions.
IgG is the most abundant immunoglobulin and constitutes 75 percent of serum immunoglobulin in an adult human

Anti-nuclear antibodies(ANAs) also referred to as anti-nuclear factors (ANFs) are autoantibodies that bind to contents of the cell nucleus. They can be of any immunoglobulin class.

CREST syndrome is usually associated with anti-centromere antibodies.

ELISA testing is cheaper but not the most accurate means of testing for ANAs. Indirect immunofluorescence testing is the most reliable.

Nucleolar staining is suggestive of scleroderma, while homogenous staining is suggestive of lupus.

Anti-dsDNA antibodies are found in 80 – 90% of patients with SLE

A papule is a solid, well circumscribed, skin elevation measuring less than 0.5 cm in diameter.

A nodule is a solid, well circumscribed, raised area that lies in or under the skin and measures greater than 0.5 cm in diameter. They are usually painless.

A bulla is a visible collection of clear fluid measuring greater than 0.5 cm in diameter.

A furuncle, or boil, is a pyogenic infection of the hair follicle commonly caused by infection with Staphylococcus aureus.

A pustule is a small visible skin elevation containing an accumulation of pus.

Blood transfusion can be a life-saving treatment with significant clinical benefits, but it also comes with a number of risks and potential complications, including:
Immunological side effects
Errors in administration (episodes of ‘wrong blood’)
Viruses and Infections (bacterial, viral, possibly prion)
Immunodilution

A culture of better safety procedures as well as steps to reduce the use of transfusion has emerged as a result of growing awareness of avoidable risk and improved reporting systems. Transfusion errors, on the other hand, continue to occur, and some serious adverse reactions go unreported.

Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare blood transfusion complication that causes fever, rash, and diarrhoea 1-4 weeks after the transfusion. Pancytopenia and liver function abnormalities are common laboratory findings.

TA-GVHD, unlike GVHD following allogeneic marrow transplantation, causes profound marrow aplasia with a mortality rate of >90%. Survival is uncommon, with death occurring within 1-3 weeks of the onset of symptoms.

Because of immunodeficiency, severe immunosuppression, or shared HLA antigens, viable T lymphocytes in blood components are transfused, engraft, and react against the recipient’s tissues, and the recipient is unable to reject the donor lymphocytes.
The following is a list of the most common transfusion reactions and complications:

1) Reaction to a febrile transfusion
The temperature rises by one degree from the baseline. Chills and malaise are also possible symptoms.
The most common response (1 in 8 transfusions).
Cytokines from leukocytes in transfused red cell or platelet components are usually to blame.
Only supportive. The use of paracetamol is beneficial.

2) Acute haemolytic reaction is a type of haemolytic reaction that occurs when the
Fever, chills, pain at the transfusion site, nausea, vomiting, and dark urine are all symptoms of a transfusion reaction.
Early on, many people report a sense of ‘impending doom.’
The most serious reaction. ABO incompatibility is frequently caused by a clerical error.
STOP THE TRANSFUSION OF INFORMATION. IV fluids should be given. It’s possible that diuretics will be required.

3) Haemolytic reaction that is delayed
It usually happens 4 to 8 days after a blood transfusion.
Fever, anaemia, jaundice, and haemoglobinuria are all symptoms that the patient has.
Positive Coombs test for direct antiglobulin.
Because of the low titre antibody, it is difficult to detect in a cross-match, and it is unable to cause lysis at the time of transfusion.
The majority of delayed haemolytic reactions are harmless and do not require treatment.
Anaemia and renal function should be monitored and treated as needed.

4) Reaction to allergens
Foreign plasma proteins are usually to blame, but anti-IgA could also be to blame.
Urticaria, pruritus, and hives are typical allergic reactions. It’s possible that it’s linked to laryngeal oedema or bronchospasm.
Anaphylaxis is a rare occurrence.
Antihistamines can be used to treat allergic reactions symptomatically. It is not necessary to stop transfusions.
If the patient develops anaphylaxis, the transfusion should be stopped and the patient should be given adrenaline and treated according to the ALS protocol.

5) TRALI (Transfusion Related Acute Lung Injury)
Within 6 hours of transfusion, there was a sudden onset of non-cardiogenic pulmonary oedema.
It’s linked to the presence of antibodies to recipient leukocyte antigens in the donor blood.
The most common cause of death from transfusion reactions is this.
STOP THE TRANSFUSION OF INFORMATION. Oxygen should be given to the patient. Around 75% of patients will require aggressive respiratory support.
The use of diuretics should be avoided.

6) TACO (Transfusion Associated Circulatory Overload)
Acute or worsening respiratory distress within 6 hours of a large blood transfusion. Fluid overload and pulmonary and peripheral oedema can be seen. Rapid blood pressure rises are common. BNP is usually 1.5 times higher than it was before the transfusion. It is most common in the elderly and those who have chronic anaemia.

Blood transfusions should be given slowly, over the course of 3-4 hours.

Basophils are only occasionally seen in normal peripheral blood comprising < 1% of circulating white cells. However, they are the largest type of granulocyte. They have many dark cytoplasmic granules which overlie the nucleus and contain heparin and histamine. They have immunoglobulin E (IgE) attachment sites and their degranulation is associated with histamine release. Basophils are very similar in both appearance and function to mast cells.

Functional hyposplenism is characterised by the blood film findings of Howell-Jolly bodies or siderotic granules on iron staining. The most frequent cause is surgical removal of the spleen e.g. after traumatic rupture, but hyposplenism can also occur in sickle cell anaemia, gluten-induced enteropathy, amyloidosis and other conditions.

C-reactive protein (CRP) is an acute phase protein produced by the liver hepatocytes. Its production is regulated by cytokines, particularly interleukin 6 (IL-6) and it can be measured in the serum as a nonspecific marker of inflammation.

Although a high CRP suggest an acute infection or inflammation, it does not identify the cause or location of infection.

Approximately 400 red blood cell group antigens have been described. The ABO group antigens are unusual in that naturally occurring antibodies occur in the plasma of subjects who lack the corresponding antigen, even if they have not been exposed to that antigen previously. The most important of these natural antibodies are anti-A and anti-B, which are usually IgM. Anti-D antibodies don’t occur naturally, and are therefore immune antibodies that result from previous transfusions or pregnancy. Only IgG antibodies are capable of transplacental passage and the most important immune antibody is the Rh antibody, anti-D.

Acute haemolytic transfusion reactions present with: Feeling of ‘impending doom’ as the earliest symptom, fever and chills, pain and warmth at transfusion site, nausea and vomiting, back, joint, and chest pain. Transfusion should be stopped immediately and IV fluid (usually normal saline) administered.

Supportive measures and paracetamol can be given since patient has fever but it is not the immediate first step.

A macule is a flat, well circumscribed area of discoloured skin less than 1 cm in diameter with no changes in the thickness or texture of the skin.

A vesicle is a visible collection of clear fluid measuring less than 0.5 cm in diameter.

A papule is a solid, well circumscribed, skin elevation measuring less than 0.5 cm in diameter.

A nodule is a solid, well circumscribed, raised area that lies in or under the skin and measures greater than 0.5 cm in diameter. They are usually painless.

A plaque is a palpable skin lesion that is elevated and measures >1cm in diameter.

Coagulative necrosis is the most common form of necrosis characterised by the loss of cell nuclei, but with general preservation of the underlying architecture. Dead tissue is macroscopically pale and firm. This is the classic pattern seen in myocardial infarction.Liquefactive necrosis leads to complete loss of cellular structure and conversion into a soft, semi-solid mass. This is typically seen in the brain following cerebral infarction.Caseous necrosis is most commonly seen in tuberculosis. Histologically, the complete loss of normal tissue architecture is replaced by amorphous, granular and eosinophilic tissue with a variable amount of fat and an appearance reminiscent of cottage cheese.Gangrenous necrosis is necrosis with putrefaction of tissues due to exposure to air (dry gangrene) or infection (wet gangrene).

Delayed haemolytic transfusion reactions (DHTRs) commonly occurs 4-8 days after blood transfusion, but can occur up to a month after. Signs and symptoms include jaundice, fever, an inadequate rise in PCV, reticulocytosis, a positive antibody screen and a positive Direct Antiglobulin Test (Coombs test). DHTRs usually have a benign course and require no treatment but sometimes, life-threatening haemolysis with severe anaemia and renal failure can occur so haemoglobin levels and renal function should be monitored.

Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.

Febrile transfusion reaction presents with a 1 degree rise in temperature from baseline during transfusion. Patient may have chills and malaise. It is the most common transfusion reaction (1 in 8 transfusions) and is usually caused by cytokines released from leukocytes in transfused red cell or platelet components.

Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.

Graft versus host disease(GVHD) is an immune mediated condition that arises from a complex interaction between donor and recipients adaptive immunity. It presents as dermatitis, hepatitis and enteritis developing within 100 days after stem cell or bone marrow transplant.

Non-specific signs of anaemia include:
1. pallor of mucous membranes or nail beds (if Hb < 90 g/L),
2. tachycardia
3. bounding pulse
4. wide pulse pressure
5. flow murmurs
6. cardiomegaly
7. signs of congestive cardiac failure (in severe cases)

Laboratory findings typically show (although this varies depending on VWD type):
Abnormal PFA-100 test
Low factor VIII levels (if low a factor VIII/VWF binding assay is performed)
Prolonged APTT (or normal)
Normal PT
Low VWF levels
Defective platelet aggregation
Normal platelet count

Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer that primarily affects children. ALL is most common between the ages of 2 and 4, and it is uncommon in adults.

Classic signs:
Rubor (redness)
Calor (heat)
Dolour (pain)
Tumour (swelling)
Functio laesa (loss of function)
These classic signs are produced by a rapid vascular response and cellular events. The main function of these events is to bring elements of the immune system to the site of injury and prevent further tissue damage.