Pathology Flashcards
What is inheritance and genotype of sickle cell anaemia?
Autosomal recessive
Sickle cell anaemia - HbSS
Sickle cell trait - HbAS
What is the management of transfusion related acute lung injury?
STOP THE TRANSFUSION.
Oxygen should be administered. Approximately 75% of patients require aggressive respiratory support.
Diuretic usage should be avoided
What transfusion product is most likely to result in bacterial infection?
What is the most common bacteria to be associated with transfusion infections?
Platelets - as stored at room temp
The most common bacterial organism associated with transfusion is Yersinia enterocolitica. This organism is capable of multiplying at low temperatures and using iron as a nutrient.
In Polycythaemia vera is arterial or venous thrombosis more common?
Arterial
What are the criteria for a diagnosis of Polycythaemia vera?
The diagnosis of PCV requires two major criteria and one minor criterion, or the first major criterion and two minor criteria:
Major criteria:
HB > 18.5 g/dl in men, 16.5 g/dl in women
Elevated red cell mass > 25% above mean normal predicted value
Presence of JAK2 mutation
Minor criteria:
Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic and megakaryocytic proliferation
Serum erythropoietin level below normal range
Endogenous erythroid colony formation in vitro
What is poikilocytosis?
Abnormalities of red cell shape are referred to as poikilocytosis.
What are Heinz bodies?
List 5 conditions where they are seen?
‘Heinz bodies’ are denatured haemoglobin caused by oxidative damage. They appear as small, round inclusions within the red cell body.
They are never seen in normal, healthy individuals because they are removed by the spleen.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency NADPH deficiency Chronic liver disease Alpha thalassaemia Hyposplenism or asplenia
What is the mutation causing sickle cell disease?
A point mutation in the beta-globin chain of haemoglobin, causing glutamic acid to be replaced by valine at the sixth position.
The beta-globin gene is found on chromosome 11.
What are Target cells?
In what conditions might they be seen?
‘Target cells, which are also known as codocytes or ‘Mexican hat cells’ have the appearance of a shooting target with a bullseye.. These cells are characterized by a disproportional increase in the ratio of the surface membrane area to volume.
Liver disease Alpha thalassaemia Beta thalassaemia Haemoglobin C disease Post-splenectomy Autosplenectomy caused by sickle-cell disease
Sickle cell disease patient presents with pleuritic pain in left hypochondrium radiating to left shoulder, audible rub over the area.
What is the complication he has?
Splenic infarction
What is the inheritance pattern of the Thalassaemias?
Which populations tend to have them?
Autosomal recessive
They are commonest in people of Mediterranean and Asian origin
What are Howell-Jolly bodies?
When are they seen?
Nuclear remnants found in red blood cells that are normally removed by the spleen.
Appears as a basophilic (purple) spot on the otherwise eosinophilic (pink) erythrocyte.
They are usually seen in conditions where splenic function has been markedly decreased: Post-splenectomy Splenic trauma Autosplenectomy secondary to sickle-cell disease Amyloidosis Severe haemolytic anaemia Severe megaloblastic anaemia Myelodysplastic syndrome
What is Glanzmann’s thrombasthenia
Glanzmann’s thrombasthenia is a rare platelet disorder in which platelets contain defective or low levels of glycoprotein IIb/IIIa.
Glycoprotein IIb/IIIa is a receptor for fibrinogen
What kind of anaemia are pencil cells typical of?
Iron deficiency anaemia
What are cigar cells otherwise known as?
In what conditions are they seen?
‘Cigar cells’, also known as elliptocytes, are red blood cells that have an oval or elongated stretched out shape.
Most commonly associated with hereditary elliptocytosis but may also be seen in iron deficiency anaemia, myeloproliferative disorders and myelodysplastic syndromes.
What is the inheritance pattern of G6PD deficiency?
What can trigger a haemolytic crisis?
X-linked recessive
Illness, most notably infection and DKA
Drugs including certain antibiotics, antimalarials, sulphonamides and aspirin
Foods, most notably fava beans
What antibiotics can trigger a haemolytic crisis in G6PD deficiency?
Nitrofurantoin
Quinolones (such as ciprofloxacin)
Trimethoprim
Chloramphenicol
The use of penicillins and cephalosporins is safe however, and does not trigger haemolysis.
Can girls be affected by G6PD deficiency?
Symptomatic patients are almost exclusively male but females can occasionally be affected due to unfavourable lyonisation.
Lyonization theory states that in the somatic cells of female mammals, one of the two X chromosomes is randomly inactivated early in development
What is the most common type of transfusion reaction?
Febrile transfusion reaction
What factor is deficient in Haemophilia A?
What inheritance pattern does it have?
Factor VIII
Usually X-linked recessive
How does ITP present?
What causes it?
Immune mediated reduction in platelet count.
Antibodies target glycoprotein IIb-IIIa or Ib complex.
Acute ITP is more common in children and has an equal sex distribution. Chronic ITP is more common in young to middle aged women.
ITP tends to present with epistaxis, oral bleeding, purpura or petechiae and not usually with haemarthrosis.
It is also not an inherited disorder.
What is the most common hereditary coagulation disorder?
Von Willebrand disease (vWD) is the most common hereditary coagulation disorder occurring in approximately 1 in 100 of the population.
Deficiency in Von Willebrand factor (vWF)
This causes a reduction in factor VIII levels as vWF binds to factor VIII to protect it from rapid breakdown within the blood.
vWF is also required for platelet adhesion and a deficiency of it will also result in abnormal platelet function.
Prolongs both the APTT and the bleeding time
If symptomatic the most common symptoms are easy bruising, epistaxis and menorrhagia.
What inheritance is shown by Factor V Leiden mutation?
Autosomal dominant
Results in a hypercoagulable state
Trisomy 21 is associated with which leukaemia?
ALL
How is Transfusion-associated circulatory overload (TACO) managed?
In many cases simply slowing the transfusion rate, placing the patient in an upright position, and administering diuretics will suffice. In more severe cases the transfusion should be stopped and non-invasive ventilation considered.
What are Rouleaux?
What conditions are associated?
Rouleaux are stacks or aggregations of red blood cells caused by the presence of high levels of circulating acute-phase proteins, which increase red cell ‘stickiness’.
They are often an indication that a patient has a high ESR.
Infections/sepsis Autoimmune conditions e.g. rheumatoid arthritis Multiple myeloma Waldenstrom’s macroglobulinaemia Malignancy
What is the mechanism behind an allergic reaction to transfusion?
Allergic reactions occur when patients have antibodies that react with foreign plasma proteins in transfused blood components.
What is the most common type of adult leukaemia?
CLL
What is the predominant cell lineage seen in CLL?
Who tends to get the disease?
Approximately 95% of cases are of B-cell lineage.
> 75% of patients that present with CLL are men over the age of 50.
What kind of anaemia does hypothyroidism cause?
Macrocytic anaemia
What is the leading cause of transfusion related deaths in the UK?
TRALI
accounting for approximately one-third of all transfusion related deaths.
The transfusion should be stopped immediately and oxygen administered. Respiratory support, such as NIV or intubation and ventilation, is often required. Diuretics should be avoided and there is no evidence for the use of corticosteroids.
What is Wiskott-Aldrich syndrome?
A rare X-linked recessive disorder that results in the production of small platelets that do not function properly. These platelets are therefore removed by the spleen, resulting in thrombocytopenia.
Characterized by: Thrombocytopaenia Bloody diarrhoea Eczema Immune deficiency
How is vWD treated?
Desmopressin can be used to treat bleeding in mild cases of von Willebrand disease. This works by raising the patient’s own levels of vWF by releasing vWF that is stored in the Weibel-Palade bodies in the endothelial cells. The Weibel-Palade bodies are the storage granules of endothelial cells that form the inner lining of the blood vessels and the heart.
More severe cases are treated with replacement therapy using cryoprecipitate infusions or Factor VIII concentrate. Replacement therapy is advised for patients with severe von Willebrand’s disease that are having moderate or major surgical procedures performed.
Translocation occurs between which chromosomes in Philadelphia chromosome?
Which leukaemia is it most common in?
Balanced translocation between chromosomes 9 and 22
The Philadelphia chromosome is a balanced translocation between chromosomes 9 and 22.
It is most commonly seen in chronic myeloid leukaemia (CML), being present in over 90% of cases.
It carries a poor prognosis if seen in adult AML.
It is also present in 25% of adult ALL cases and 5% of childhood ALL cases.
What clotting factor is deficient in Haemophilia B?
What is the inheritance pattern?
clotting factor IX
X-linked recessive fashion, affecting males born to carrier mothers.
Which condition has a variation called Leyden?
A variation of Haemophilia B called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.
What is Leukaemia cutis?
Leukaemia cutis is the infiltration of neoplastic leukocytes in the skin.
It occurs in approximately 10% of patients with AML.
What is the cause of Paroxysmal nocturnal haemoglobinuria?
How can a definitive diagnosis be made?
Caused by a haematopoietic stem cell mutation defect of the PIGA gene on the X-chromosome. In PNH there is a marked deficiency or absence of the complement regulatory proteins CD55 and CD59.
This mutation results in increased sensitivity of the cell membranes to the action of the patient’s own complement, which damages red cells, white cells, platelets and stem cells. This in turn, results in intravascular haemolysis with haemoglobinuria, leukopenia and thrombocytopenia.
Thrombosis tends to affect veins.
A definitive diagnosis can be made using flow cytometry to detect the complement regulatory proteins CD55 (DAF) and CD59 (MIRL). Absence or reduced expression of both CD55 and CD59 is diagnostic for PNH.
Reed-Sternberg cells indicate what condition?
Hodgkin’s lymphoma - multinucleated giant cells, owl’s eye nuclei
The peak incidence is in young adults aged 20-35, and there is a slight male predominance.
Most patients present with an enlarged, but otherwise asymptomatic lymph node.
Other common clinical features include shortness of breath and chest discomfort secondary to mediastinal mass.
Pain after alcohol consumption is a pathognomonic sign of Hodgkin’s lymphoma
What clinical staging is used in 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
What is the most common type of Hodgkin’s lymphoma?
Nodular sclerosing
Lymphocyte-depleted and lymphocyte-predominant are rare subtypes.
Which condition is a/w Anti-Ro and Anti-La?
Sjögren’s syndrome
Which condition is a/w Anti-Jo1?
polymyositis and dermatomyositis
Which 3 groups of beta haemolytic Strep are important in humans?
A, B, D
Rash of target lesions, started on hands, spread to torso. What is it and what is most common cause?
Erythema multiforme
HSV
What is MGUS?
MGUS is a condition where paraprotein is present but below threshold and without skeletal involvement. This can progress to Myeloma in 10-30% of cases.
What is the infectious period of measles?
From 4 days before rash to 4 days after
What is the normal range for anion gap and how is it calculated?
The normal range = 10-18 mmol/L
Na+ + K+) - (Cl- + HCO-3
What are the 4 types of hypersensitivity reaction?
Type 1 - allergy (immediate), IgE
Type 2 - cytotoxic/antibody dependent
Type 3 - immune complex mediated
Type 4 - delayed
Give 3 examples of type 4 hypersensitivity reactions?
Contact Dermatitis
Mantoux test
Multiple Sclerosis
What stain is used to show PCP following BAL?
Silver stain
What is the management of PCP?
co-trimoxazole
IV pentamidine in severe cases
steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)
What is Rheumatoid factor?
RF is an antibody (IgM) directed against IgG (Fc Portion)
What are the 3 drugs used in combination to treat Hep C?
pegylated interferon-alpha, ribavirin and a protease inhibitor (e.g. boceprevir, simeprevir and telaprevir)
Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic
What kind of HSV is responsible for 95% of cases of Herpes Simplex Encephalitis?
What is the treatment?
HSV-1
Often affects temporal and inferior frontal lobes
intravenous aciclovir
Measles incubation period?
10-18 days
What is the most common cause of viral gastroenteritis in children <5 years?
Rotavirus
What is p53?
What chromosome is it on?
Which 3 cancers is it involved in?
p53 is a tumour suppressor gene located on chromosome 17p.
It is the most commonly mutated gene in breast, colon and lung cancer
What are the 3 Dermatophytes that commonly cause skin disease in humans?
Tinea corporis (Ringworm of the body) Tinea pedis (Athlete's foot) Tinea capitis (Scalp ringworm)
What is the treatment for Chlamydia?
Azithromycin 1g as a stat dose is appropriate 1st line treatment.
Doxycycline 100mg BD for 7 days is an alternative but compliance should be considered as a longer course is required.
