Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y5 Blood > List I - Core Conditions > Flashcards

List I - Core Conditions Flashcards

1
Q

What is macrocytosis?

A
  • MCV >96fL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a megaloblast?

A
  • A cell in which nuclear maturation delayed compared to cytoplasm (occurs with B12 and folate deficiency as both are required for DNA synethesis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is folate absorbed / used in the body?

A
  • Green vegetables, nuts, yeast, liver
  • Synthesized by gut bacteria
  • Absorbed by duodenum/proximal jejunum
  • Body stores for at least 4 months
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is B12 absorbed / used in the body?

A
  • Meat, fish, dairy products (not plants)
  • Require 2mcg/day
  • B12 is protein bound so released during digestion
  • Binds to intrinsic factor in the stomach
  • This complex is absorbed in the terminal ileum
  • Body stores last 4 years
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is macrocytosis caused by?

A
  • Megaloblastic anaemia
  • B12 deficiency (pernicious anaemia - 5% but most common cause in the West), folate deficiency, cytotoxic drugs
  • Non-megaloblastic anaemia
  • Alcoholism (often without accompanying anaemia), reticolocytosis (e.g. haemolysis), liver disease, hypothyroidism, pregnancy, cytotoxic drugs
  • Other haematological disease
  • Myelodysplasia, myeloma, myeloproliferative disorders, aplastic anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the causes of folate deficiency?

A
  • Poor diet - poverty, alcoholics, elderly
  • Increased demand - pregnancy, increased turnover (haemolysis, malignancy, inflammatory, renal dialysis)
  • Malabsorption - coeliac disease, tropical sprue
  • Others - drugs, alcohol, phenytoin/valproate, methotrexate, trimethoprim
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the causes of B12 deficiency?

A
  • Poor diet - vegan
  • Malabsorption - stomach (lack of intrinsic factor): pernicious anaemia (autoimmune atrophic gastritis - achlorydia, lack of intrinsic factor secretion), post gastrectomy, terminal ileum: ileal resection, Crohn’s disease, bacterial overgrowth, tropical sprue, tapeworm
  • Congenital - abnormalities in metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the risk factors for pernicious anaemia?

A
  • Other autoimmune conditions - (thyroid 25%. vitiligo, Addisons, hypoparathyroidism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How common is macrocytosis / pernicious anaemia?

A
  • Macrocytosis - common

* Pernicious anaemia - 1:1000, F:M 1/6:1, >40 years usually, increased incidence in blood group A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the pathophysiology of deficiency in folate / B12?

A
  • Folate deficiency - maternal deficiency can cause neural tube defects
  • B12 deficiency - impairs synthesis of thymidine (DNA) is impaired so reduced RBC production
  • Subacute combined degeneration of the spinal cord (B12 deficiency) - combined symmetrical dorsal column loss (sensory/LMN signs) and symmetrical corticospinal tract loss (motor/UMN signs) but NB pain/temperature usually normal as spinothalamic tract often preserved
  • Myelodysplasia - oval macrocytes with anisocytosis and poikilocytosis and small fragmented cells (schistocytes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the symptoms and signs of macrocytic anaemia?

A
  • Generally similar to IDA
  • Signs (B12 deficiency)
  • General - lemon tinge to skin from both anaemia pallor and haemolytic jaundice), glossitis (beefy red, sore tongue), angular cheilosis (aka stomatitis)
  • Psychiatric - irritability, depression, psychosis, dementia,
  • Neurological - paraesthesiae, peripheral neuropathy
  • Subacute combined degeneration of the spinal cord (SACDS) - insidious onset, first joint position/vibration affected (ataxic gait: falls at night) - stiffness/weakness if untreated (classic triad of: extensor plantar response from UMN loss, absent knee jerks from LMN loss, absent ankle jerks from LMN loss)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the differentials for macrocytic anaemia?

A

Other causes of glossitis:

  • Iron/zinc deficiency
  • Pellagra
  • Contact dermatitis/food intolerance
  • Crohn’s
  • Coeliac
  • Drugs (minocycline, clarithromycin, some ACEi’s)
  • Alcoholism
  • Tongue TB (ulcers, fissures, tuberculoma, diffuse glossitis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the appropriate blood investigations for macrocytic anaemia?

A
  • Bloods - FBC (low Hb, high MCV, severe pernicious anaemia also low WCC, low platelets) should normalise within a week with therapy
  • Serum B12 and folate (or red cell folate - more reliable indicator of folate status as serum folate only reflects recent intake), reticulocytes (low or normal in pernicious anaemia)
  • Blood film - B12/folate deficiency (hypersegmented >5 segments - neutrophil polymorphs), liver disease (target cells)
  • U and E’s - observed for low K+ as therapy becomes established
  • LFT including GGT
  • TFT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the special tests for macrocytic anaemia?

A
  • Bone marrow biopsy if cause not revealed from blood tests
  • Megaloblastic - B12/folate deficiencies
  • Normoblastic - liver disease, hypothyroidism
  • Abnormal erythropoiesis - sideroblastic anaemia, leukaemia, aplastic anaemia
  • Increased erythropoiesis (haemolysis)
  • Pernicious anaemia screen - parietal cell Abs (90%), intrinsic factor Abs
  • Small bowel biopsy - to look for small bowel malabsorption (if <40 years)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the conservative approach to management of macrocytic anaemia?

A
  • Lifestyle - improve dietary intake
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the medical approach to management of macrocytic anaemia?

A
  • Treat the cause - injections if malabsorption
  • Oral supplements - folic acid 5mg/24h po for 4 months plus either cyanocobalamin (B12) 50-150mcg/24h po between meals (if folate deficiency and low B12) - NB giving folic acid in the presence of low B12 can precipitate SADC, or if B12 deficiency due to poor diet - leave out the folic acid - or hydroxycobalamin (B12) 1 mg/48 h IM (for 2 weeks if very ill with folate deficiency - e.g. CCF or for 2 weeks then maintained at 1mg IM every 3 weeks for life if pernicious anaemia and having sent the blood tests off)
  • NB - improvement by transient increased MCV - due to reticulocytosis - after 4-5 days, additional iron may be needed
  • Blood transfusions - rarely needed (indicated if severely symptomatic or Hb < 7-8)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the complications of macrocytic anaemia?

A
  • Risk of pernicious anaemia - increase x 3 of gastric cancer, irreversible CNS complications (as for simple B12 deficiency)
  • Prognosis - oral supplements improve peripheral neuropathy in 3-6 months (little effect on cord signs), earlier treatment = better prognosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How is macrocytic anaemia prevented?

A
  • Pregnancy
  • Folate supplementation 400mcg/24 po (from conception until at least the last 12 weeks - to prevent spina bifida as well as anaemia)
  • Women at higher risk of conceiving a child with a NTD should take 5mg of folic acid from before conception until the 12th week of pregnancy
  • Women are considered higher risk if the any of the following apply:
  • Either partner has a NTD, previous pregnancy affected by NTD, or FH NTD
  • Woman is taking anti-epileptic drugs or has coeliac disease, diabetes, or thalassaemia trait
  • Woman is obese (BMI 30 kg/m2 or more)
  • Cognition - if borderline folate deficiency (shown by increase in homocysteine), folic acid 800mcg/24hrs po for 3 years may benefit cognition
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is haemolysis?

A
  • Premature breakdown of RBC’s before normal life span of 120 days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is haemolytic anaemia?

A
  • When bone marrow cannot compensate for haemolysis
  • Intra-vascular - within circulation
  • Extra-vascular - within reticulo-endothelial system (liver, spleen, bone marrow)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the acquired causes of haemolytic anaemia?

A
  • Drug induced - penicillin/quinine
  • Auto-immune - occuring at body temperature, IgG mediated, splenic phagocytes, cold: occurring when cold, IgM mediated
  • Paroxysmal cold Hb uria - with viruses/syphilis
  • Acute transfusion reaction
  • Haemolysis of newborn
  • Microangiopathic haemolytic anaemia (MHA)
  • Haemolytic uraemic syndrome - e.coli infection, deficiency of complement factor H, triad of acute renal failure, MHA and thrombocytopenia
  • Thrombotic thrombocytopenic purpura - TTP: red cell fragments in blood, thrombocytopenia, neurological abnormalities, renal impairment, fever
  • DIC
  • Pre-eclampsia
  • Mechanical heart valves - shearing
  • Infection - malaria, viruses/syphilis
  • Paraoxysmal nocturnal Hb-uria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the inherited causes of haemolytic anaemia?

A
  • G6PD - x-linked, African/Mediterranean/Middle Eastern, needed to maintain glutathione (protects RBC’s against oxidative injury), neonatal jaundice, triggered by sulphonamides/aspirin/fava beans/henna, pyruvate kinase deficiency
  • Autosomal recessive - reduced ATP production causes short RBC survival, childhood jaundice/anaemia and splenomegaly
  • Hereditary spherocytosis - autosomal dominant, membrane dysfunction (makes them rounder, less pliable) become stuck in spleen/haemolysed, childhood jaundice/splenomegally
  • Sickle cell anaemia
  • Thalassaemia

Triggers - infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the pathophysiology of haemolytic anaemia?

A
  • Occurs either intravascular (in the circulation) or extravascular (in reticuloendothelial system: macrophages of liver, spleen, bone marrow)
  • Sickle cell anaemia - life span as short as 5 days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the symptoms of haemolytic anaemia?

A
  • Asymptomatic
  • SOB
  • Lethargy
  • Pallor
  • Dark urine
  • Jaundice

PMH - previous anaemia
DH - medications
FH - Gilbert’s syndrome, ethinicity
SH - recent travel - malaria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the signs of haemolytic anaemia?

A
  • Jaundice
  • Pallor
  • Splenomegaly (extravascular)
  • Hepatomegaly
  • Gallstones (pigmented from increased bilirubin)
  • Leg ulcers (poor blood flow)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the differentials / how is diagnosis of haemolytic anaemia made?

A

Consider what is happening? - what could the cause be?

  • Increased RBC breakdown - low Hb, increased MCV, increased unconjugated bilirubin, increased urinary urobilinogen (as no urinary conjugated bilirubin), increased LDH (released from RBC’s)
  • Increased RBC production - high reticulocytes, causes high MCV, polychromasia (RBC’s of different ages stain differently)
  • Mainly extravascular or intravascular
  • Extravascular - splenic hypertrophy/splenomegaly
  • Intravascular - increase in free plasma Hb (released from RBC’s), methaemalbuminaemia (haem combined to albumin), low plasma haptoglobin (as mops up free Hb, removed by liver), Hb-uria (red brown urine, in absence of RBC’s), haemosiderinuria (when haptoglobulin-binding capacity exceeded
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the appropriate blood investigations for haemolytic anaemia?

A
  • FBC (low Hb, high MCV, low platelets: HUS, increased reticulocytes)
  • LFT (increase unconjugated bilirubin)
  • LDL (increase as released from RBC’s)
  • Haptoglobin (increase)

Blood film

  • Hypochromic/microcytic (thalassaemia)
  • Sickle cell (SCA)
  • Schistocytes (MHA)
  • Abnormal cells (haematological malignancy)
  • Polychromasia (RBC different ages, stain differently)
  • Heinz bodies/bite cells/blister cells (G6PD)
  • Prickle cells (pyruvate kinase deficiency)
  • Sperocytes (hereditary spherocytosis/autoimmune haemolytic anaemia)
  • Elliptocytes (hereditary elliptocytosis)
  • Thick/thin films (malaria)

Direct Coombes test (direct antiglobulin test)
* Detects Abs/complement against RBC’s that are actually on the RBC’s (by adding anti-human Abs - Coombes reagent +ve test indicates an immune mediated cause (e.g. autoimmune haemolytic anaemia)

Indirect Coombes test (pre-natal testing/before blood transfusion, detect Abs against RBC’s that are free in the serum (by adding donor sample to recipients and using Coombes reagent)

G6PD enzyme assay
* After acute attack to exclude G6PD

Hb electrophoresis
* To detect haemoglobinopathies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the urine tests for haemolytic anaemia investigation?

A
  • MSU - dipstick (Hb-uria - if intravascular)

* Assay - urobilinogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the principles of management of haemolytic anaemia?

A
  • Auto-immune haemolytic anaemia - steroids, immunosuppression, splenectomy, avoid the cold
  • HUS - supportive treatment, volume plasmapheresis and anti-coagulation
  • TTP - Plasmapheresis and infusion of FFP (20% mortality)
  • G6PD - prevented by avoiding the precipitants, transfusion during the attack
  • Pyruvate kinase deficiency - folate, transfusion, splenectomy
  • Hereditary sperocytosis - normally requires splenectomy after the age of 5, life long prophylactic penicillin
  • Thalassaemia - lifelong blood transfusions (causes iron overload - risk pituitary dysfunction/DM/cardiac toxicity - so give chelator desferrioxamine), splenectomy, marrow transplant may offer a cure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is lymphoma?

A
  • Blood disorder caused by malignant proliferations of lymphocytes and precursor cells (Hodgkin’s and NH are defined according to histology - Hodgkin’s has Reed Sternberg Cells)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the causes / risk factors for developing Hodgkin’s lymphoma?

A
  • Cause - unknown
  • Risk factors - affected sibling x 7 risk increase, EBV (33% may alter host immunity), SLE, post transplant, Weternisation, obesity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How common is Hodgkin’s lymphoma?

A
  • 2-3/100,000 in Western Europe (rare)
  • 1500/year in UK
  • 2 peaks (18-35 yrs, >60 yrs)
  • M:F = 2:1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the pathophysiology of Hodgkin’s lymphoma?

A
  • Malignant proliferation of lymphocytes
  • Lymph node accumulation (lymphadenopathy - consisting malignant lymphocytes but also reactive T-lymphocytes and polymorphs)
  • May infiltrate peripheral blood or organs
34
Q

What are the histological findings of Hodgkin’s lymphoma?

A
  • Characteristic malignant mononuclear Hodgkin’s cells or multinucleated Reed-Sternberg Cells (transformed B-lymphocyte with 2 mirror image nuclei - seen in 97%) of histological subtypes:
    1) Nodular sclerosing (75%) most common form, especially in younger patients, better prognosis (limited subdiaphragmatic disease)
    2) Mixed cellularity (25%) many different cell lines (often subdiaphragmatic disease
    3) Lymphocyte predominant (rare) strongly lymphocytic stroma with fewer malignant cells, indolent course, late relapses
    4) Lymphocyte depleted (least common) few lymphocytes, more malignant cells, especially in older patients/more advanced/poor prognosis
    5) Nodular lymphocyte predominant new subtype with frequent relapses/remissions, 5-10% risk of progressing to NHL (large B cell lymphoma)
35
Q

What are the symptoms of Hodgkin’s lymphoma?

A
  • Superficial lymph nodes
  • Cervical 60-70%, axillary, inguinal
  • Enlarged painless, non-tender, rubbery, size (may increase / decrease spontaneously), can become matted
  • Systemic (25%)
  • B symptoms - weight loss > 10% in last 6 months, drenching night sweats - needing change of clothes, fever >38c - may also have Pel-Ebstein fever which is cyclical with long periods of normal/low temperature often 15-28 days, others (pruritis, lethargy, alcohol induced lymph node pain, weakness)
  • Pressure symptoms
  • Especially mediastinal lymphadenopathy: more commonly in young adults with nodular sclerosing
  • Bronchial/SVC obstruction
  • Direct extension symptoms
  • Pleural effusions
  • Extra nodal (very late manifestation)
  • Skin, brain, lung
36
Q

What are the signs of Hodgkin’s lymphoma?

A
  • Painless asymetrical lymp node enlargement, cachexia, anaemia, splenomegaly (50%), hepatomegaly
37
Q

What are the blood investigations for Hodgkin’s lymphoma?

A
  • FBC (low Hb: normochromic, normocytic, increased WCC in 33%, platelets normal but then decrease)
  • U and E’s (pre-chemotherapy)
  • LFT’s (increased, released in cell turnover: high ALP, GGT and bilirubin increase if biliary obstruction at porta hepatis, Alb < 4 has poor prognosis), ESR increased, LDH increased (poor prognosis), increased urate, hypercalacaemia
  • Blood film
38
Q

What are the radiological investigations for Hodgkin’s lymphoma?

A
  • Chest x-ray - signs of mediastinal involvement

* CT chest, abdomen, pelvis - for staging

39
Q

What are the special tests available for Hodgkin’s lymphoma?

A
  • Diagnostic tissue biopsy - either lymph node excision biopsy (if possible) or image guided needle core biopsy (not FNA)
  • Bone marrow trephine biopsy - if B symptoms present, advanced disease (stage III/IV disease) or unexplained abnormal haematology
40
Q

What staging system is used for Hodgkin’s lymphoma?

A 
* Ann Arbor Staging
I - single lymph node
II - 2 or more lymph nodes/regions on same side of diaphragm
III - Nodes on both sides of diaphragm
IV - Spread beyond lymph nodes

Each stage may be divided into A or B

  • A = no systemic symptoms other than pruritus
  • B = weight loss >10% in last 6 months, fever >38c, night sweats (poor prognosis)

Hence ‘B’ symptoms

41
Q

What is the medical approach to the management of Hodgkin’s lymphoma?

A
  • Radiotherapy - good for small volume (e.g. lymphocte predominant)/good prognosis (stage I-IIA)
  • If relapse can give high dose chemotherapy (w/o affecting prognosis by much - so chemotherapy alone in stage I-IIA disease not justified)
  • Combination chemotherapy (ABVD - adriamycin, bleomycin, vinblastine, dacarbazine): good for stage IIB or worse disease (and radiotherapy in younger patients - More intense regimes if poor prognosis/advanced disease
  • For younger patients with excellent prognosis offer sperm banking, high dose chemotherapy with peripheral stem cell transplant
  • For relapsed disease (use autologous/allogenic or peripheral blood progenitor cells to restore marrow function after therapy
42
Q

What are the possible complications of Hodgkin’s lymphoma?

A
  • Emergency complications - neutropenic sepsis, SVCO (RJVP, sense of fullness in head, SOB, blckouts, facial oedema)
  • Risk of
  • Radiotherapy 2nd malignancy (solid lung/breast/melanoma/sarcoma/stomach/thyroid), IHD, hypothyroidism, lung fibrosis
  • Chemotherapy - myelosuppression, nausea, alopecia, infection, AML, non-Hodgkin’s lymphoma, infertility
43
Q

What is the prognosis of patients with Hodgkin’s lymphoma?

A
  • Good - 80% cure rate if ABVD chemotherapy regime is used
  • Poor - if large mediastinal mass (>33% throacic width on chest x-ray or >10cm on CT), extranodal involvement, increased ESR, (>30 for B or >50 for A), >3 lymph node areas, B symptoms, albumin <4, Hb low <10.5
44
Q

What is the mortality of patients with Hodgkin’s lymphoma?

A
  • 5 year survival - >95% (stage IA lymphocyte predominant disease) or <40% (stage IVB lymphocyte depleted)
45
Q

What is non-hodgkin’s lymphoma (NHL)?

A
  • Includes all lymphomas without Reed-Sternberg cells
  • Represents a very diverse group of diseases, most of which are derived from B lymphocyte cell lines but T cell lines are also seen
46
Q

What are the NHL subtypes?

A
  • Based on histology
  • Low grade - follicular lymphoma e.g. B cell FL or cutaneous T cell lymphoma, marginal zone lymphoma (including MALT lymphoma associated with H.pylori, regresses when eradicated), lymphocytic lymphoma (closely related to CLL), lymphoplasmacytoid lymphoma (production of IgM = Waldenstroms macroglobuminaemia)
  • High grade - Burkitt’s lymphoma (childhood disease with characteristic jaw lymphadenopthy), lymphoblastic lymphoma (similar to ALL), diffuse large B cell lymphoma (DLBCL)
47
Q

What are the causes of NHL?

A
  • Chromosomal abnormalities (85% acquired because non-germ line): 14:18 translocation (follicular B-cell lymphoma - over expression of bel-2, translocation of 8:14 (Burkitt’s lymphoma)
48
Q

What are the risk factors for NHL?

A
  • Viruses - EBV (Burkitt’s lymphoma), human T cell leukaemia virus type 1 (HTLV-1: aggressive T cell lymphoma)
  • Immunosuppression (1 or acquired) - EBV (has a role in B cell lymphomas usually), HIV (usually high grade lymphomas), transplant associated lymphoproliferative disease
  • H. Pylori - mucosa associated lymphoid tissue (MALT) lymphoma usually
  • Auto-immune disease - coeliac disease (T cell lymphomas of intestine), Hashimoto’s thyroiditis
49
Q

How common is NHL?

A
  • 1/10,000 (doubled since 1970’s)
  • 7000/year in UK (>4000 NHL related deaths/year)
  • Median age 55 years
  • Mostly B cell type
50
Q

What is the pathophysiology of NHL?

A
  • Low grade - widely disseminated at presentation, indolent (thus prolonged survival) - 7-8 years), non-destructive growth patterns, rarely involving the CNS, often incurrable
  • High grade - short hx of rapidly enlarging lymph node with systemic symptoms, more aggressive, destructive growth patterns, often involving CNS/extra nodal tissue, long term cure may be achievable (although rapidly fatal without treatment)
51
Q

What are the presenting symptoms/signs of NHL?

A
  • Nodal disease (75%)
  • Painless enlargement of superficial lymph node
  • Extra-nodal disease (up to 50%)
  • Oropharynx (Waldeyer’s ring: sore throat, obstructed breathing, skin (facial erythema - cutaneous T cell lymphomas), bone, GI tract (ascites - end stage), CNS, lung (pleural effusions -usually end stage), thyroid, testis
  • Systemic - fever, night sweats, weight loss (less common than Hodgkin’s, indicates disseminated disease), pruiritis
  • Pancytopenia (due to bone marrow involvement) - anaemia (SOB, fatigue, etc), neutropenia (infection), thrombocytopenia (bleeding)
52
Q

What are the appropriate blood investigations for NHL?

A
  • FBC (Hb low, normochromic normocytic, then with progressive marrow infiltration, reduced WCC, especially neutrophils and platelets)
  • U and E’s (pre chemotherapy)
  • LFT’s (increased, released in cell turnover: high ALP, GGT and bilirubin increase if biliary obstruction at porta hepatis, ESR increased, LDH increased (poor prognosis), increased beta microglobulin, increased urate, hypercalacaemia
  • Blood film
53
Q

What are the radiological investigations for NHL?

A
  • Chest x-ray - signs of mediastinal involvement
  • CT/MRI chest, abdomen and pelvis - for staging
  • CT head if needed
  • Radionucleotide bone scan if needed
54
Q

What are the special tests that can be done for NHL?

A
  • Diagnostic tissue biopsy - either by lymph node excision biopsy (if possible) or image guided needle core biopsy (not FNA)
  • Bone marrow trephine biopsy/aspiration - for staging (and immuno-phenotyping/cytogenetic analysis)
  • Pleural tap for effusion - send for cytology
  • LP for CSF cytology if any CNS signs
55
Q

What is the staging system for NHL?

A
  • Ann Arbor as for Hodgkin’s lymphoma
56
Q

What is the approach to managing low grade NHL?

A
  • None - if symptomless (or eradication therapy for h.pylori if MALT)
  • Radiotherapy - may be curative in localised disease (>50% disease free >10 years later)
  • Chemotherapy - oral chlorambucil (diffuse disease)
  • Biologicals - alpha interferon (40% response rate, 10-15% cure rate), rituximab (to maintain remission: bendamustine with rituximab - anti-CD10 Ab - or if refractory to it)
57
Q

What is the approach to managing high grade NHL?

A
  • Combination therapy (R-CHOP regime - 80% response rate, 30-40% cure rate) rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine (Onconvin), prednisolone
  • High dose chemotherapy - for relapses or primary resistant disease (or poor prognosis at presentation)
  • Granulocyte stimulating factors - help neutropenia e.g, filgrastim/lenograstim
  • Surgical not for therapeutic intervention (unless advanced gastric lymphoma)
58
Q

What are the possible complications of NHL?

A
  • Risk from accumulation of lymphoid tissue - mediastinal obstruction, obstructive neuropathy, spinal cord compression, meningeal lymphoma, bone marrow failure
  • Para-neoplastic syndromes - hypercalacaemia, immune related haemolysis/thrombocytopenia (low grade)
59
Q

What is the prognosis of NHL?

A
  • Poor if - age >60, systemic symptoms, bulky disease (abdo mass >10 cm), LDH raised, disseminated disease (stage III/IV), extra nodal involvement at >1 site, performance status >2
60
Q

What is the mortality of NHL?

A
  • 5 year survival for treated patients - 30% high grade - 1/3 are cured and >50% low grade - median survival is 7-8 years
61
Q

What is multiple myeloma (MM)?

A
  • Haematological malignancy characterised by plasma cell proliferation
  • Arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells
  • MM is the second most common malignancy
  • Median age at presentation is 70 years old
62
Q

How does MM present?

A
  • Mnemonia CRABBI can be used to identify the systems affected:
  • Calcium
  • Hypercalacaemia occurs as a result of increased osteoclast activity within the bones
  • Leads to constipation, nausea, anorexia and confusion
  • Renal
  • Monoclonal production of Ig’s results in light chain deposition with the renal tubules
  • Causes renal damage which presents as dehydration and increasing thirst
  • Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
  • Anaemia
  • Bone marrow crowding suppresses erythropoiesis leading to anaemia
  • Causes fatigue and pallor
  • Bleeding
  • Bone marrow crowding also results in throbocytopenia which puts patients at increased risk of bleeding and bruising
  • Bones
  • Bone marrow infiltration by plasma cells and cytokine mediated osteoclast overactivity creates lytic bone lesions
  • May present as pain (especially in the back) and increases the risk of fragility fractures
  • Infection
  • Reduction in the production of normal immunoglobulins results in an increased susceptibility to infection
63
Q

What is a plasma cell?

A
  • B-lymphocyte derived Ig producing cells, normally identifiable in bone marrow
64
Q

What happens with plasma cells in MM?

A
  • Diffuse malignant monoclonal proliferation of plasma cells throughout red bone marrow
65
Q

How is MM classified?

A
  • Based on production of Ig: IgG (2/3), IgA (1/3), IgM/D (small remainder)
66
Q

How common is MM?

A
  • 5/100,000/year in the UK
  • Median age 60-70 years (<2% occur <40 years)
  • M:F = 1:1
  • Afro-Carribbeans: Caucasians = 2:1
67
Q

What is the pathophysiology of MM Ig production and problems this can cause?

A
  • Malignant production of plasma cells
  • Plasma cells synthesise paraprotein
  • Monoclonal Ig (99% cases: consists of IgG 60%, IgA 20%, light chain only 20% and rarely IgM, IgD)
  • Monoclonal free light chains (kappa/lambda) are produced in addition to the complete Ig molecule (66% of IgG/A myelomas)
  • These free light chains can pass through the glomerulus (excreted in urine as ‘Bence Jones’ proteins, but Igs cannot
  • Plasma (unaffected Igs) often suppressed (immunoparesis - increases susceptibility to infection)
68
Q

How does the malignant proliferation of plasma cells affect the body in MM?

A
  • Inappropriate activation of osteoclasts
  • Lytic erosions of bones of axial skeleton
  • Increased risk of pathological fractures of proximal long bones, ribs, sternum, vertebrae
  • Can lead to spinal cord compression with infiltration of paravertebral tissues
  • Anaemia (chronic disease - predisposes to amyloidosis, low erythropoietin
  • Renal failure from free light chains especially Tamm-Horsfall protein in distal loop of Henle, bone marrow failure
  • Neutropenia/thrombocytopenia (from marrow infiltration)
  • Hyperviscosity (seen with IgA myeloma due to physical characteristics of IgA paraprotein)
69
Q

What are the signs and symptoms of MM?

A
  • Bone pan - common, severe
  • do serum electrophoresis and ESR on all >50 years with back pain*
  • Back ache, pathological fractures (long bones, ribs, vertebrae), vertebral collapse
  • Anaemia - SOB, lethargy, pallor
  • Neutropenia - recurrent infection
  • Thrombocytopenia - bleeding
  • Renal impairment (20%) - polydipsia, polyuria, anorexia, vomiting
  • Hypercalacaemia - stones (renal, ectopic calcification), bones, moans (depression, tiredness, weakness, confusion) and abdominal groans (abdo pain, vomiting, constipation, anorexia, weight loss, polyuria, polydipsia)
  • Hyperviscosity syndrome (rare) - confusion, blurred vision
  • Amyloidosis - carpal tunnel syndrome, macrglossia
70
Q

How is a diagnosis of MM made?

A
  • Requires one major criteria and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma
  • Major criteria
  • Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
  • 30% plasma cells in bone marrow sample
  • Elevated levels of M protein in the blood or urine
  • Minor criteria
  • 10% to 30% plasma cells in a bone marrow sample
  • Minor elevations in the level of M protein in the blood or urine
  • Osteolytic lesions (as demostrated on imaging studies)
  • Low levels of antibodies (not produced by cancer cells) in the blood
71
Q

What is the mechanism of hypercalcaemia in myeloma?

A
  • Primary factor - due primarly to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
  • Much less common contributing factors- impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels
72
Q

What are the blood investigations for MM?

A
  • FBC (low Hb: normochromic, normocytic)
  • PV raised
  • ESR raised, serum electrophoresis (identifies intact paraprotein - usually IgG/A - may only be free light chain, or none at all i.e. non secretory myeloma)
  • Blood film - rouleaux formation: RBC’s stuck on each other
  • U and E’s - high urea/creatinine: renal impairment
  • Hypercalacaemia (40%)
  • LFT - normal ALP unless healing fracture but low albumin associated with poor prognosis
73
Q

What are the urine investigations for MM?

A
  • Bence-Jones protein (in 2/3 cases - cannot see on urine dipstick)
74
Q

What are the radiological investigations that can be done for MM?

A
  • Whole body MRI (NICE 2016) - skull, chest, pelvis, proximal long bones - to identify lytic lesions - punched out lesions, vertebral collapse, fractures, osteoporosis
  • X-rays - RAIN DROP SKULL (likened to pattern rain forms after hitting a surface and splashing, leaving random pattern of dark spots)
  • NB very similar but subtly different finding is found in primary hyperparathyroidism - ‘pepper pot’ skull
75
Q

What special tests are done for investigating MM?

A
  • Bone marrow aspiration - shows patchy/variable levels of infiltration by plasma cells (10-40%)
76
Q

What further investigations can be done for MM?

A
  • Bloods - serum beta2-microglobulin (B2M: prognostic marker), LDH (prognostic marker), CRP (prognostic marker)
  • Radiology - MRI to identify bone disease, marrow infiltration, suspected cord compression
  • Staging (based on B2M and albumin)
    I - B2M <3.5mg/L and alb >35g/dL (median survival 62 months)
    II - Neither I nor II (median survival 45 months)
    III - B2M >5.5mg/L (median survival 29 months)
77
Q

What are the aims of management of MM?

A
  • Provide therapy for symptomatic complications

* No treatment required if no bony lesions and asymptomatic - just surveillance

78
Q

What is the conservative approach to management of MM?

A
  • Patient education/support - PIL, analgesia (avoid NSAID’s as already at risk of renal impairment), spinal supports if lytic bone lesions
  • Fluids - if new onset renal impairment / hypercalacaemia (IV 0.9% NaCl 4-6 L/day)
  • Packed red cell transfusion - severe anaemia
  • IV broad spectrum antibiotics - severe infection
79
Q

What is the medical approach to the management of MM?

A
  • Chemotherapy (57% response rate, 12% 5 yr survival): mephanan +/- prednisolone (if >65yrs provided neutrophils >1x10(9)/L and plts >75 x 10(9)/L - otherwise cyclophosphamide
  • High dose chemotherapy (VAD) and stem cell transplant (81% response rate, 52% 5 yr survival): vincristine, doxorubicin (Adriamycin), dexamethasone followed by high dose melphanan and stem cell transplant (if <65 yrs)
  • Bisphosphonates (osteoclast inhibitors): routine therapy for hypercalacaemia, prevent pathological vertebral fractures and reduced bone related pain
  • Localised radiotherapy - if localised disease e.g. solitary plasmacytoma of bone or spinal cord compression from malignant infiltration of vertebrae
80
Q

What is the surgical approach to the management of MM?

A
  • Orthopaedic surgery (vertebroplasty/kyphoplasty)
  • Long bone fixation reserved for patients with pathological fractures (or prophylactically for patients with impending fractures)
81
Q

What are the risks of complications in MM?

A
  • Pathological fractures (vertebral, long bone - treat with zolendronate/palmidronate)
  • Spinal cord compression (5% get urgent MRI if suspected - treat with 16mg dexamethasone/24 hr po and local radiotherapy)
  • Acute renal failure (treat with fluids and urgent dialysis if needed)
  • Hyperviscosity syndrome - reduced cognition, disturbed vision, bleeding - treat with plasmapheresis to remove light chains
82
Q

What is the prognosis of MM?

A
  • Poor if age >80 yrs, high LDH, high B2M, low albumin, mitotic activity (s-phase) of bone marrow plasma cells
  • Mortality - median survival is 3-4 yrs (62/45/29 months for stages I, II, III respectively) - death commonly due to renal failure / infection

Y5 Blood (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions