what are the 3 key physiological events that occur with the onset of bleeding?
2. platelet aggregartion to form PRIMARY HAEMOSTATIC PLUG
3. activation of clotting cascade to form a fibrin plug (SECONDARY HAEMOSTATIC PLUG)
where are platelets formed?
megakaryocytes in bone marrow
platelets: anucleate, but cytoplasm has electron dense granules, lysosomes, mitochondria
what is the half life of platelets in blood?
where are clotting factors made?
what converts fibrinogen to fibrin?
what prevents over-clotting of the blood by degrading fibrin?
why do women in pregnancy have a physiological anaemia?
due to increased circulating plasma volume
if pregnant women have Hb<10.5g/l what should they be given?
is B12 deficiency common in pregnancy?
no vary rare. due to excess alcohol
what are the histological findings of pernicious anaemia?
atrophy of gastric mucosa so failure of IF and gastric acid production (achlorhydria) and so B12 malab
what is the schilling's test?
what 2 types of anaemia are associated with coeliac disease?
iron deficiency anaemia
megaloblastic anaemia: folate, B12 deficiency
what type of cells are characteristic for megaloblastic anaemia?
what is aplastic anaemia?
pancytopenia in the absence of reticulocytes
bone marrow failure: hypocellular
what types of anaemia do chronic alcoholics tend to have?
megaloblastic anaemia: due to the toxic effect of alcohol on erythropoiesis or dietary folate deficiency
what is a megaloblast?
RBC in which nuclear maturation is delayed compared with the cytoplasm so you get hypersegmented neutrophils (immature)
give 3 causes of megaloblastic anaemia
B12 (cobalamin) deficiency
give 4 causes of non megaloblastic microcytic anaemia
haemolytic anaemia: get reticulocytosis
pregnancy: increased demand from foetus
what is the underlying mechanism for megaloblastic anaemia?
defective DNA synthesis so get hypersegmented neutrophils, leucopenia, thrombocytopenia, MCV > 110
what are the clinical features of B12 deficiency anaemia?
glossitis: beefy red sore tongue
lemon tinge to skin - pallor (anaemia), jaundice (haemolysis)
paraesthesia, peripheral neuropathy
depressed, irritable, psychosis
subacute combined degeneration of the spinal cord (not seen in folate deficiency): peripheral neuropathy, optic atrophy (vision changes), dementia, both symmetrical DC loss (LMN signs) and symmetrical corticospinal tract loss (UMN signs) so get classic triad of extensor plantar reflex (UMN) (positive babinski), absent knee jerk (LMN), absent ankle jerk (LMN)
why do patients with untreated B12 deficiency anaemia tend to fall at night?
subacute combined degeneration of the spinal cord - get ataxia due to JOINT POSITION and vibration sense affected and optic atrophy (reduced vision)
Why are pain and temperature sensation still in tact?
spinothalamic tracts are not affected
what is the MCV and MCHC like in anaemia of chronic disease?
normocytic normochromic anaemia
in chronic diseases such as RA, what kind of anaemias can you get?
take NSAID - gastritis and chronic blood loss - microcytic hypochromic anaemia (IDA)
normocytic normochromic anaemia (ACD)
what test is done to detect AIHA?
Direct antiglobulin test (Coombs' test): detects autoAb on surface of red cells
what are features of a blood film in haemolytic anaemia?
normocytic normochromic anaemia
what would be found in the blood of haemolytic anaemia?
what is the difference between warm and cold AIHA?
temperature at which Ab attaches better to the RBC
cold: lower than 37
what causes warm AIHA? which Ab mediates it?
bind at body temp 37 degrees
autoimmune diseases: eg SLE
lymphoproliferative disease: e.g. CLL, lymphoma
What causes cold AIHA? which Ab?
bind at lower temp <4degrees, activating cell surface complement
following infection e.g. mycoplasma pneumonia, EBV
what is the treatment of warm AIHA?
steroids or immunosuppressants (think autoimm disease and lymphoprolif)
what is the treatment of cold AIHA?
chlorambucil may help
what are the hereditary causes of haemolytic anaemia?
RBC enzyme defect: glucose-6phosphate dehydrogenase deficiency. asymp but susceptible to oxidative crisis due to reduced glutathione prod precip by drugs, fauvism; pyruvate kinase deficiency
membrane defect: hereditary spherocytosis - less deformable spherical RBC so trapped in spleen - extravasc haemolysis
Hb defect: sickle cell, thalassaemia
what are the consequences of parvovirus B19 infection?
aplastic anaemia due to BM stops working
adults: gets better on own.
children: slapped cheek syndrome - bright red rash over cheeks
what is the blood film and symptoms like in G6PD deficiency attack?
oxidative crises - so oxidised denatured Hb - form Heinz bodies
bite cell and blister cell: after removal of Heinz body by spleen.
what cells are present in Hodgkin's lymphoma?
Reed-Sternberg cells: have mirror image nuclei (2nuclei)
what are the 2 peaks of incidence of hodgkins lymphoma?
how does lymphoma present?
enlarged PAINLESS non tender rubbery LN - cervical or axillary or inguinal (the superficial ones)
in Hodgkins lymphoma, what can induce LN pain?
what can mediastinal LN involvement in HL cause?
mass effect: bronchial or SVC obstruction
direct extension: causing pleural effusion
why do you get lymphadenopathy in lymphomas?
malignant proliferation of lymphocytes which accumulate in LN
what are the investigations needed for HL?
blood: FBC, film (RSC), LDH (raised as inc cell turnover), Ca, urate, LFT, high ESR, low Hb worse pro
tissue diagnosis: LN excision biopsy
what is the Rx for HL?
chemo, radio or both (SE both: AML, NHL, infertility)
stem cell transplantation
radio SE: solid tumours (lung, breast, thyroid) near radiation field, IHD, hypothyroid, lung fibrosis