4th May [22nd-30th] Flashcards
1
Q
Where is most calcium in the body stored?
A
99% in the bones as calcium phosphate
2
Q
Breakdown of calcium in cells?
A
0.01% in cells, 0.99% in the extracellular spaces like the blood
3
Q
What can high intercellular calcium cause?
A
Apoptosis
4
Q
Where is the extracellular calcium found?
A
Diffusible
- free-ionised: hormone secretion, muscle contraction, blood coagulation
- complexed: calcium oxalate, electronically not neutral cellular prcoess
Non-diffusible
- albumin and calcium; too large to diffuse into cells
5
Q
How are extracellular levels controlled?
A
Parathyroid cell detects change in level -> parathyroid hormone has various actions:
- Bones release calcium
- kidneys reabsorb calcium
- calcitriol [active vitamin D]-> GI absorbs calcium
6
Q
How can acidosis cause symptoms of hyperacalcaemia?
A
Normally, parathyroid hcells keeps calcium between 8.5-10mg/dL.
However, albumin has nehative COOH groups and if increased H+ the COOH- groups pick up excess H+ and become positively charged -> positive albumin sand Ca2+ now repel each other -> more free-ionised Ca2+ [as less not diffusible] = Sx of hypercalcaemia
7
Q
How can dehydration cause pseudocalcaemia? [rare]
A
In hyperalbuminaemia, more bound Ca2+ though some free-ionised Ca2+ as it is homronally regulated -> false hypercalaemia
8
Q
Two main causes of true hypercalcaemia?
A
Osteoclastic bone resorption [most common]
Excess vitamin D
9
Q
How do osteoclasts work?
A
Break down bone -> Ca2+ into the blood
10
Q
Causes of osteoclast bone resorption
A
- Can happen due to parathyroid glad overgrowth -> increased parathyroid hormone
- Malignant tumours -> secrete parathyroid hormone related protein [PTHrP]
- malignant turmours can also cause osteoclast death -> lytic bone lesions
11
Q
How can excess vitamin D happen?
A
Diet, or through supplements
- increased absorption of Ca2+ in the gut
Medications like thiazide diuretics
- increased reabsorption distal tubule
12
Q
Physiology of neurological Sx related to hypercalcaemia
A
Resting state of neurone stabilised by Ca2+ which prevents spontaneous depolarisation
In hypercalcaemia, sodium channels less liely to open
- harder to depolarise, less excitable
- slower/absent reflexes
- slow muscle contraction = constipation/general muscle weakness
- confusion/hallucinations/stupor in CNS
13
Q
Neuro Sx of hypercalcaemia
A
Slow muscle contraction
- constipation
- generalised muscle weakness
CNS
- confusion
- hallucinations
- stupor
14
Q
Nephro physiology of hyeprcalcaemia
A
High Ca2+ excreted in urine -> hypercalciuria -> loss of fluid kidneys -> dehydrated
Combination of hypercalciuria+dehydration can lead to calcium oxalate kidney stones
15
Q
Mnemonic for primary hyperparathyroidism [think also for hypercalcaemia]
A
Bones, stones, abdominal groans, psychic moans
16
Q
Diagnosing hypercalcaemia
A
Elevated Ca2+ in the blood [over 10.5mg/dL] Electrocardiogram - OSBORN wave - short QT wave - bradycardia - AV block
Lab tests
- parathyroid, vitamin D, albumin, phosphorus, magnesium
17
Q
Treating hypercalcaemia
A
lower calcium in the blood
- increase urinary excretion with hydration [more Ca2+ filtered], loop diuretics [inhibit Ca2+ reabsorption]
- increased GI excretion -> glucocorticoids -> decrease Ca2+ absorption
- prevent bone resorption: bisphosphonates+calcium => inhibit osteoclasts
18
Q
Treating acute hypercalcaemia [handbook]
A
- Correct dehydration [if dehydrated, give 0.9% saline]
- Bisphosphonates: prevent osteoclast activity. Single dose pamidronate lowers calcium over 2-3d, maximum effect at 1 week. Zoledronate acid usually single dose effective at 90mg.
- Further Mx: chemo to help malignancy, steroid used in sarcoidosis [eg prednisolone 40-60mg/d], salmon calcitonin acts similarly to bisphosphonates but now rarely used. Use of furosemide cententious helps Ca2+ renal excretion but cna worsen dehydration and so worsen hypercalcaemia. Should only be used once fully rehydrated. Avoid thiazides.
19
Q
What is the haematocrit?
A
Ratio of RBC in the total blood volume
Normally, around 45%.
20
Q
How common is the JAK2 mutation in PV?
A
90%
21
Q
What produces erythropoietin?
A
Kindeys
22
Q
How does erythropoietin work?
A
- Activates the JAK2 gene
- mutation keeps the JAK2 gene activated, even in the absence of erythropoeitin
- becomes dominant haemopoeitic stem cell in bone marrow
23
Q
How can PV lead to myelofibrosis?
A
As haemapoetin stem cells become dominant in the bone marrow, cells start to die out
- this leads to scar tissue
- BM can no longer produce RBCs -> decrease in RBCs/plts/WCC
- known as spent phase in decreased RBC -? myleofibrosis
24
Q
Sx of PV early stages
A
fatigue itching [esp. hot showeer due to increased eosinophils and basophils] trouble breathing when you lie down trouble concentrating unplanned weight loss pain in your abdomen feeling easily full blurred or double vision dizziness weakness heavy sweating bleeding or bruising
25
Sx of PV in later stages
As the disease progresses and your blood becomes thickened with more red blood cells, more serious symptoms can appear, such as:
```
heavy bleeding from even minor cuts
swollen joints
bone pain
reddish color to your face
bleeding gums
burning feeling in your hands or feet
splenomegaly
buildup of kidney stones
more prone to strokes/heart attacks/DVT/Budd-Chiari
```
26
Blood tests done for PV
Bloods
- increased haemoglobin, increased haematocrit, increased WBC, increased plts
- decreased erythropoeitin
- BM biopsy for fibrosis
- genetic test for JAK2 mutation
27
Tx for PV
- Phlebotomy: can't be used for donations, but can be used for autologous transplantation [such as in spent phase]
- Myelosuppressive medication: hydroxyuria, ruxolitinib [JAK2 inhibitor]
- antihistamines, apsirin etc.
28
Where do lymphoma cancers arise from?
Tumours derived from lymphocytes which are B cells or T cells
29
Broadly, what are lymphomas categorised into?
Hodgkins
| Non-hodgkins
30
Main differences between HL and NHL
Hodgkins
- arise from B cells generally
- spread contiguously to nearby lymph nodes, rarely involving extra nodal sites
- bimodal ages: 20s, and over 60s
- Reed-Sternberg cells [owl eyes] B cells
NHL
- B/T-cells
- more common with 90% of cases [I think]
- spreads non-contiguously and involved in extra-nodal sites like skin/brain/GI
- prognosis worse
31
Compare B-cell to T- cell NHL
B-cell
- more common
- neoplastic B-cells express CD20
- various types [growth rate]: 1. Follicular 2. Burkitt 3. Mantle cell 4. MZL
- can be indolent, aggressive, highly aggressive
T-cell
- less common
- types include: 1. LPL 2. Adult T-cell 3. MF
32
Define myeloproliferative disorders
Group of cancers where there's an excess of RBCs, WBCs, plts produced by the bone marrow
33
Main categories of myeloproliferative disorders [with accompanied mutations]
1. CML - > Philadelphia chromsome [BCR-ABL]
2. CNL -> CSF3R gene, excl. other cancers
3. PV -> JAK2 mutation
4. PMF -> JAK2, CALR, MPL
5. ET -> 450x109/L plts
6. Chronic eosinophilic leukemia -> PDGFR
7. MPN, unclassifiable [MPN-U] -> Dx of exlcusion
8. Mastocytosis
34
Common population myeloproliferative disorders found in?
Mainly the elderly
35
Which blood components are affected in myeloproliferative disorders?
RBCs, WBCs, plts are all affected, however one dominant in each disorder
36
How can myeloproliferative disorders lead to attacks of gout?
rapid cell turnover -> nucleus -> pruein metabolism -> increased uric acid -> precipitate attacks of gout
37
What can all myeloproliferative disorders progress onto?
Acute myeloid luekemia [secondary]
38
Which mutation do PV, PMF and ET all share?
V617F mutation -> activation of JAK2 kinase
39
How does JAK2 kinase work in myeloproliferative disorders?
- JAK2 kinase stimulates erythropoietin and thrombopoeitin in receptors but not GM-CSF
- So EPO and TPO decrease as negative feedback ensues
40
What can a pluripotent haematopoeitic stem cell turn into? Disorder where this can go wrong?
1. Myeloid stem cell
2. Lymphoid stem cell
Disorder = PMF
41
What can a myeloid stem cell turn into?
| Disorders where they can go wrong?
1. Pro-erythroblast -> erythrocyte [PV]
2. Myelobalst -> basophil/neutrophil/eosinophil [CML]
3. Monoblast -> monocyte
4. Megakaryoblast -> megakaryocyte -> plts [ET]
42
What can lymphoid stem cells turn into?
1. B -cells
2. T-cells
3. natural killer cells
43
How high are plts in ET?
over 450
44
If patient is under 60 y/o, what would you tend to give them?
interferon-gamma
45
Mutations in ET?
JAK2, CALR, MPL mutation
46
Dx for ET
Platelet count
| Also, exclusion to rule out CML, reactive causes, iron deficiency anaemia
47
Ix for ET?
CRP/ESR for infection, blood count for platelet numbers, genetic testing, iron/ferritin, BCR-ABL for CML
48
Tx for ET
- hydroxycarbamide, inteferon gamma, anagrelide can reduce platelets
- aspirin
- plateletpharesis -> if platelets are very high
49
Sx of CML
Splenomegaly, increased WCC, fatigue
50
Main Ix for CML
BCR-ABL
51
Which stage are most patients diagnosed with CML?
Asymptomatic stage
52
What symptom may upper quadrant pain signify in a patient with CML?
Splenomegaly
53
What is the main Tx for CML?
Tyrosine kinase inhibitors
| - dasasatinib, netoinib
54
What is the first-line for myelpfibrosis?
Imitinib
55
What is cholesterol embolisiton?
Ruptured atherosclerotic plaque from a large artery
56
How is the M-spike created in myeloma?
1 cancerous cell proliferates and produces lots of monoclonal antibodies
57
How can the light chains of antibodies be divided?
Into kappa and lambda regions
58
in an infection, how do the light chains in antibodies repsond?
equal ratio of lambda and kappa
59
in myeloma, how do light chain antibodies respond?
unequal ratio [over 1] of kappa and lambda
60
How is myeloma commonly diagnosed?
Eletectrophoresis looking at the number of antibodies and comparing it to albumin
Comparing kappa and lambda regions on the antibody light chains.
61
What does MGUS stand for?
Monoclonal gammopathy of undetermined singificance
62
Mnemonic for pancreatitis?
```
I - idiopathic
G - gallstones
E - ethanol
T - trauma
S - steroids
M - mumps/malignancy
A - autoimmune
S - scorpion
H - hyperglycerides/hypercalcaemia
E - ERCP [post]
D - drugs [azathioprine, pentamidine, bactrim]
```
63
Which blood disorder can menstruating women suffer from?
Menstruating women x6 more likely to get iron deficiency anaemia
64
Causes of low platelets
1. Failure of central production
- leukemia
- dysplasia
- AA
2. Peripheral consumption
- DIC
- ITP
- sepsis
- HIT
- TTP
- ITP [generate platlets to own antibodies]
65
What is ITP?
Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of other causes of low platelets.[1] It causes a characteristic red or purple bruise-like rash and an increased tendency to bleed. Two distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults. The acute form often follows an infection and spontaneously resolves within two months. Chronic immune thrombocytopenia persists longer than six months with a specific cause being unknown.
ITP is an autoimmune disease with antibodies detectable against several platelet surface structures.
66
What is TTP?
Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in blood clots forming in small blood vessels throughout the body.[2] This results in a low platelet count, low red blood cells due to their breakdown, and often kidney, heart, and brain dysfunction.[1] Symptoms may include large bruises, fever, weakness, shortness of breath, confusion, and headache.[2][3] Repeated episodes may occur.[3]
67
What is melphalan?
Alkylating agent used against myeloma
Nitrogen bases and used as mustard gas in WW1
Works by interfering with creation of DNA/RNA
68
DVD drug therapy
Darzalex, velcade and dexamethasone
69
Type of cancer is multiple myeloma?
B cell cancer [plasma cells]
70
Sx of MM?
Often no Sx initially -> bone pain, anaemia, kidney dysfunction develops
71
What is the condition which MM often originate from?
MGUS
72
CRAB mnemonic for MM
C: calcium over 2.75mmol/l
R: renal creatinine over 40
A: anaemia over 10g/dl
B: bone lesions on radiography
73
How common is bone pain?
In 70% of patients it's present
74
Type of anaemia in MM?
Normocytic
75
Neuro symptoms of MM
Hypercalcaemia
- weakness
- confusion
- fatigue
Hyper-viscosity
- headache
- vision
- retinopathy
Neuropathy
- radicular pain
- bowel
- bladder
- carpal tunnel
- peripheral neuropathy may occur with Tx for MM
76
RFs for MM
MGUS
Obesity
FHx
EBV [particularly those with immunodeficiency]
77
Dx for MM
```
Protein electrophoresis of the blood/urine which might show M bands
IgG most common, then IgA/IgM
IgD and E rare
Raised calcium and creatinine
Biopsy
```
78
Criteria for Dx of MM
1. Clonal plasma cells above 10%
2. Monoclonal protein over 3g/dL
3. Evidence of end-organ damage in CRAB
79
Chemotherapy drug classes
1. Thalidomide
2. Steroid
3. Monoclonal
4. Protease inhibitor [-nib]
5. Alkylating agents
80
Define thrombocytopenia
Platelet count under 150,000/mm3
81
What are platelets made by?
Megakaryocytes
82
How many platelets does each megakaryocyte mkae?
1-5k
83
Normal physiology of a blood clot
1. Vasoconstriction [platelet/wWF]
2. Platelet plug [adhesion onto exposed collagen, activation, aggregation]
3. Coagulation [clotting factor activation causes prothrombin to thrombin etc.]
84
What is platelet production stimulated by?q
Thrombopoeitin and inflammation from cytokines like IL-6
85
How many platelets are sequestered in the spleen at any one time?
1/3rd
86
How long do platelets live for?
about 7d
87
How are platelets removed in the body?
Platelets removed by monocytes of the reticuloendothelaial system [i.e. liver/spleen]
88
Causes of thrombocytopenia
1. Reduced platelet production: bone marrow disroders [like failure, acute leukemia, malignancy, alcohol whihc can all lead to disruption in thrombopoeisis], ITP
2. Increased platelet consumption: DIC, TTP/HUS, HIT
3. Splenomegaly: portal hypertension, Felty's syndrome [such as seen in RA]
4. Dilatational: massive fluid resuscitation
5. Increased platelet destruction: ITP [when antibodies attack platelets]
Infection common cause which can lead to many different causes of thrombocytopenia
89
Skin Sx of thrombocytopenia
Purpura, petechia
90
Other Sx of thrombocytopenia
Mucosal bleeding, lymphadenopathy, splenomegaly/hepatomegaly, fever, loss of appetite
