Key elements of the maturation stage include collagen cross-linking, collagen remodelling, wound contraction, and repigmentation. The tensile strength of the wound is directly proportional to the amount of collagen present. Numerous types of collagen have been identified; types I and III predominate in the skin and aponeurotic layers. Initially, a triple helix (tropocollagen) is formed by three protein chains; two are identical alpha-1 protein chains, and the third is an alpha-2 protein.

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

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

The composition of immunoglobulin molecules is two identical heavy and two identical light chains. These chains are linked by disulphide bridges and are each have highly variable regions which give the immunoglobulin its specificity. In addition, they have constant regions and there is virtual complete correspondence in amino acid sequence in all antibodies of a given isotype.
Five isotypes of immunoglobulin exist – these are IgG, IgA, IgM, IgE and IgD. They are determined by the heavy chain (gamma, alpha, mu, epsilon or delta respectively). The light chains are either kappa or lambda.

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.

Eosinophils comprise 1 – 3% of circulating white cells. Eosinophils are similar to neutrophils, except that the cytoplasmic granules are coarser and more deeply red staining, and there are rarely more than three nuclear lobes. They are less motile, but longer lived. They enter inflammatory exudates and have a special role in allergic responses, defence against parasites and removal of fibrin formed during inflammation. Thus they play a role in local immunity and tissue repair.

Examples of type III reactions include:
Extrinsic allergic alveolitis
Systemic lupus erythematosus (SLE)
Post-streptococcal glomerulonephritis
Reactive arthritis
Rheumatoid arthritis

Basic healing is complete by 5-10 days but maximal wound strength (80% of normal) may take 12 weeks.

98% of cases of myeloma occur over the age of 40 years with a peak incidence between 65 and 70 years. The disease is twice as common in black individuals compared to those of white or Asian origin. Laboratory findings include presence of a paraprotein in serum/urine (the paraprotein is IgG in 60% of cases, IgA in 20% and light chain only in almost all the rest) and marked Rouleaux formation on blood film. There is no cure for myeloma. The overall median survival is now 7-10 years and in younger (less than 50 years) patients it can be over 10 years.

Sickling of red blood cells can lead to several different clinical syndromes. If the sickling occurs in the corpora cavernosa, it can lead to a sustained, painful erection of the penis, referred to as priapism. One of the complications is long-term impotence. It is important to seek a urological opinion immediately in this case, but in the interim, treat with perineal ice packs and walk up and down the stairs.

Aplastic anaemia is a life-threatening failure of haemopoiesis characterised by pancytopenia and hypocellular bone marrow. It is rare and patients present with features of recurrent infections secondary to (leukocytopenia), increased bleeding tendency (secondary to thrombocytopenia) and anaemia. In aplastic anaemia, there is damage to the bone marrow and the haematopoietic stems cells leading to pancytopenia.

Monocytes account for around 5 to 10% of peripheral white cells. Monocytes in peripheral blood are generally bigger than other leukocytes and feature a large central oval or indented nucleus with clumped chromatin. The abundant cytoplasm staining blue and containing numerous fine vacuoles gives the appearance of ground glass. Cytoplasmic granules are another type of granule.

Monocytes evolve from the granulocyte-macrophage progenitor to become monoblasts, promonocytes, monocytes, and tissue macrophages (in increasing order of maturity). Monocytes only stay in the bone marrow for a short time before exiting to circulate in the bloodstream for 20-40 hours before becoming macrophages.

Features of cell damage that tend to be reversible include: swelling of endoplasmic reticulum and some mitochondrialoss of ribosomescell stress response
Features of cell damage that tend to be irreversible include: loss of nucleolus, no ribosomes, swelling of all mitochondria, nuclear condensation, membrane blebs and holes, lysosome rupture, fragmentation of all inner membranes, nuclear breakup

Vaccination induces ACTIVE adaptive immunity. Actively acquired immunity involves the development of an immune response either due to vaccination or natural exposure to a pathogen and leads to long-lasting resistance to infection.

Immediate protection is achieved with injection of immunoglobulin. The protection is transient lasting only a few weeks and is useful as post-exposure prophylaxis.

Passively acquired immunity usually leads to short-lasting resistance to infection because it does not involve a host immune response.

With inactivated bacteria, a series of primary vaccinations is usually required to induce an adequate immune response. In most cases, boosters are required to sustain adequate immunity.

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.

The collection of abnormalities found in these patients is referred to as a hyposplenic film.
The following features can be seen on hyposplenic blood films:
Howell-Jolly bodies
Heinz’s bodies
Target cells
RBCs with nuclei on occasion
Lymphocytosis
Macrocytosis
Acanthocytes
Teardrop cells, also known as dacrocytes, are named for their teardrop-shaped shape.

Dacrocytosis is a condition in which a large number of these cells are present. Myelofibrosis and beta thalassemia major both have dacrocytes, but hyposplenism does not.

Granulomatous inflammation is a distinctive pattern of chronic inflammation that is encountered in a limited number of infectious and some non-infectious conditions. Briefly, a granuloma is a cellular attempt to contain an offending agent that is difficult to eradicate. In this attempt, there is often strong activation of T lymphocytes leading to macrophage activation, which can cause injury to normal tissues. IL-1 is important in initiating granuloma formation, IL-2 can cause them to enlarge and TNF-α maintains them.

Acute inflammation is defined as inflammation occurring within minutes to hours in response to an injury lasting for less than two weeks.

Acute inflammation
Rapid onset (minutes to hours)
Quick resolution (usually days)

Chronic inflammation
May last weeks, months, or years

There are five cardinal signs of inflammation:
1) Pain
2) Redness
3) Warmth
4) Oedema
5) Loss of function

During acute inflammation, neutrophils are activated and attracted to the site of inflammation in response to various interleukins and cytokines. This process takes place via the following mechanism:
1) Margination
Neutrophils flow nearer the vessel wall rather than in the axial stream, which is referred to as margination
2) Rolling along the surface of vascular endothelium
3) Adhesion to the endothelium by interaction with adhesion molecules (ICAMS and VCAMS)
4) Diapedesis is the movement of neutrophils from the endothelial cells into the interstitial space by squeezing through the gaps between adjacent endothelial cells

Bradykinin and histamine are both responsible for vasodilation which causes oedema and decreases intravascular osmotic pressure.

Neutrophils dominate early (<2 days)
– Many in the bloodstream
– Attach firmly to adhesion molecules
– Apoptosis after 24-48hrs
Monocytes/macrophages dominate late (>2 days)
– Live longer
– Replicate in tissues

Cytokines are a family of chemical messengers, secreted by leucocytes, that act over short distances by binding specific receptors on target cell surfaces. They include: interleukins (act between leucocytes), interferons (inhibit replication of viruses within cells and activate macrophages and natural killer cells), growth factors, and tumour necrosis factors (kill tumour cells). Effects include: induction of fever and acute phase response, stimulation of leucocyte differentiation and maturation, leucocyte recruitment and activation and increased antibody production.

Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and other lymphoid tissue and cause the characteristic clinical feature of lymphadenopathy. The major subdivision of lymphomas is into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) and this is based on the histological presence of Reed-Sternberg cells present in HL. Hodgkin lymphoma can present at any age but is rare in children and has a peak incidence in young adults. There is an almost 2 : 1 male predominance. Most patients present with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes. Cervical nodes are involved in 60-70% of cases, axillary nodes in 10-15% and inguinal nodes in 6-12%. Modest splenomegaly occurs during the course of the disease in 50% of patients; the liver may also be enlarged. Bone marrow failure involvement is unusual in early disease. The prognosis depends on age, stage and histology, but overall approximately 85% of patients are cured. Alcohol‐induced pain and pruritus are two well‐known but rare symptoms in HL.