1st June [31st-6th] Flashcards
1
Q
How to diagnose lymphoma?
A
Lymph node biopsy
2
Q
How common is non-hodgkins lymphoma?
A
About 90% of patients with lymphoma, the rest Hodgkins lymphoma
3
Q
4 main subtypes of Hodgkins lymphoma
A
- Nodular sclerosing [most common]
- Mixed cellularity
- Lymphocyte-rich
- Lymphocyte depleted
4
Q
What is a bronchoalveolar lavage?
A
Diagnostic method of the LRT with a bronchoscope
5
Q
How common are B-cell lymphomas in NHL?
A
90% of B cell lymphomas
6
Q
Name the most common types of B-cell lymphomas [NHL]
A
Diffuse large B-cell lymphoma [DLBCL]
Follicular lymphoma [FL]
7
Q
Less common types of B-cell lymphomas [NHL]
A
MALT, Mantle cell, Burkitt, nodal marginal zone B-cell etc.
8
Q
Types of T-cell lymphomas [NHL]
A
- Peripheral T cell
- Anaplastic large cell
- Cutaneous T cell lymphomas
9
Q
Type of lymphoma that can start in the brain
A
Primary central nervous system lymphomas [PCNSL] are rare and usually grow quickly
10
Q
RFs for NHL
A
Medical condition that weakens the immune system
Taking immunosuppressant medications
Previously exposed EBV
Slight increased risk if 1st degree relative
11
Q
Which chemotherapy regimen is often used for NHL?
A
R-CHOP:
R = Rituximab C = Cyclophosphamide H = doxorubicin Hydrocholoride O = vincristine [previously Oncovin] P = prednisolone
12
Q
What type of drug is rituximab?
A
Monoclonal antibody against CD20 receptor
13
Q
Aggressive types of NHL
A
DLBCL Anaplastic large cell lymphoma Burkitt lymphoma Lymphoblastic lymphoma Mantle cell lymphoma Peripheral T-cell lymphoma
14
Q
Indolent types of NHL
A
Follicular lymphoma
MALT
Cutaneous T cell
Marginal zone B-cell
15
Q
Which type of lymphoma is considered the most aggressive type of lymphoma?
A
Burkitts lympoma [B-cell NHL].
Rare, accounting for about 20% of all lymphomas.
16
Q
Why are bloods usually not that informative for lymphomas?
A
As usually normal, clinical signs like enlarged LN are seen more commonly.
17
Q
Presentation of true cutaneous T-cell lymphoma
A
Often not linear progression of skin disease [rash/lesion], will come and go
Only on the skin, does not involve LN.
18
Q
Tx for cutaneous lymphomas
A
Can be ECP [extra-corpuscle photophoresis] which involves taking blood out of the body, light exposure to T-cells, then blood back into the body.
19
Q
How does CLL typically present?
A
Early on, no Sx
Later: LN swelling, tired, fever, night sweats, weight loss etc.
20
Q
What is Scheuermann’s disease?
A
Condition in which a child has too much curvature [kyphosis] in the middle of their back.
Think it’s quite common.
21
Q
What does PCP stand for? Which populations is it prevalent in?
A
Pneumocystis pneumonia
- usually found in healthy people, though opportunistic infection in the immunocompromised such as HIV patients
22
Q
Why should you try avoiding to intubate haematology pts?
A
Low chance of success I think [5-10%]? not actually sure this is the fact though.
23
Q
Common harvest for stem cell transplant patients in caucasian populations
A
From babies umbilical cord in I think 80% of patients
24
Q
Name of process where blood is taken out of the body and then put back into the body at a later date
A
AUTOGRAPH [like signature]
25
Psychological damage caused by chemotherapy
Fatigue, depression, anxiety, cognitive fluctuating.
| Also, white matter changes can occur leading to cognitive damage/changes.
26
What are carcinoid tumours
Type of neuroendocrine tumours that affect usually small/large bowel or appendix
27
Sx of the tumour mass
Bowels
- bowel obstruction
- rectal bleeding
Lungs
- cough up blood
- chest pain
- fatigue
Stomach
- weight loss
- weakness
- loss of appetite etc.
28
Sx of the hormonal imbalance in neuroendocrine tumours
Diarrhoea
increased HR
Tumy pain
SOB etc.
29
Cure rate of Burkitt's lymphoma
About 90% in developed countries
30
Types of Burkitt lymphoma
Divided into three main subtypes:
- endemic variant ["African variant"]: most commonly children living in malaria endmic regions of the world like Africa/Brazil/New Guinea. Epstein-Barr virus found in nearly all pts. Chronic malaria is beleived to reduce resistance to EBV, allowing it to take hold. Characterised by jaw/other facial bone, ileum, cecum, ovaries, kidney, breast.
- sporadic type: most common where malaria is not holoendemic. Jaw less commonly involved, ileocecal region is commonly involved. Fast-growing, type of NHL. Most common in the UK.
- immunodefiency-associated Burkitt is usually associated with HIV infection or occurs in the setting of poast-transplant patients, can be associated with the intital manifestation of AIDS.
31
Who does sporadic Burkitt lymphoma typically develop in?
Can affect people of any age, but typically develops in children and young adults.
32
Sx of sporadic lymphoma
```
Swollen LN is the most common Sx.
Often grow in the abdomen and bowel which may cause:
- tummy/back pain
- feeling/being sick
- diarrhoea
- swelling tummy
- bleeding from bowel
- pain from blockage in bowel
```
Also, common to have B symptoms in adults such as fevers, night sweats and weight loss.
33
What do around 1 in 3 people with Burkitts lymphoma have in their bone marrow?
Have lymphoma cellls in their bone marrow which might lead to:
- anaemia: causing tiredness and SOB
- thrombocytopenia: making you more likely to bruise and bleed
- neutropenia: making it more likely for infection
34
Score for a DVT
Wells
35
Which test can e used to assist excluding the Dx or to signal further testing?
D-dimer
36
Which test is done for Dx of a DVT
Ultrasound of the suspected veins
37
Three factors imoprtant in formation of blood clot within feep vein
1. rate of blood flow
2. / Thickness of blood
3. Qualities of the vessel wall
38
What is Budd-Chiari syndreom?
blockage of the hepatic veins that drain the liver into the IVC.. Presents with abdominal pain, ascites, enlargedf liver.
39
What is cerebra; venous thrombosis?
Cerebral venous sinus thrombosis (CVST) is a rare form of stroke which results from the blockage of the dural venous sinuses by a thrombus. Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body and seizures. The diagnosis is usually made with a CT or MRI scan. The majority of persons affected make a full recovery. The mortality rate is 4.3%
40
Summarise places to get a thrombus
DVT - usually leg like femoral vein
Paget-Schoretter disease - arm after exercise
Budd-Chiari - IVC/hepatic vein
Portal vein - hepatic vein which can lead to portal hypertension
Renal vein thrombosis - reduced drainage of the kidney
Cerebral venous sinus thrombosis
Jugular vein thrombosis - from infection/IVDU/malignancy
Cavernous sinus thrombosis - cavernous sinus of the basal skull dura
Arterial thrombosis: stroke/MI
41
What are steroids made from?
Cholesterol
42
Where are corticosteroids produced from?
The adrenal cortex
43
What are the two main classes of corticosteroids?
Glucocorticoids and mineralocorticoids
44
Give an example of a glucocorticoid and a mineralocorticoid
Glucocorticoid - cortisol
| Mineralocorticoid - aldosterone
45
Function of glucocorticoids
Affect carbohydrate, fat, protein metabolism and have anti-inflammatory, immunosuppressive, anti-proliferative and vascoconstrictive effects
46
Function of mineralocorticoids
Primarily, their function is in regulation of electrolyte and water balance modulating ion transport in the epithelial cells of the real tubules of the kidney
47
Type of steroids are dexamethasone derivatives, prednisolone and its derivatives, fludrocorticone and hydrocortisone?
Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is typically used for replacement therapy, e.g. for adrenal insufficiency and congenital adrenal hyperplasia.
48
How do typical undesired effects of glucocorticoids present?
Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome.
49
How do typical SE of mineralocorticoids present
Typical mineralocorticoid side-effects are hypertension (abnormally high blood pressure), steroid induced diabetes mellitus, psychosis, poor sleep, hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema, metabolic alkalosis and connective tissue weakness.
50
Effect of immunosuppressive effects of steroids
Wound healing or ulcer formation may be inhibited by the immunosuppressive effects
51
SE of corticosteroids
Severe amebic colitis: Fulminant amebic colitis is associated with high case fatality and can occur in patients infected with the parasite Entamoeba histolytica after exposure to corticosteroid medications.[19]
Neuropsychiatric: steroid psychosis,[20] and anxiety,[21] depression. Therapeutic doses may cause a feeling of artificial well-being ("steroid euphoria").[22] The neuropsychiatric effects are partly mediated by sensitization of the body to the actions of adrenaline. Therapeutically, the bulk of corticosteroid dose is given in the morning to mimic the body's diurnal rhythm; if given at night, the feeling of being energized will interfere with sleep. An extensive review is provided by Flores and Gumina.[23]
Cardiovascular: Corticosteroids can cause sodium retention through a direct action on the kidney, in a manner analogous to the mineralocorticoid aldosterone. This can result in fluid retention and hypertension.
Metabolic: Corticosteroids cause a movement of body fat to the face and torso, resulting in "moon face", "buffalo hump", and "pot belly" or "beer belly", and cause movement of body fat away from the limbs. This has been termed corticosteroid-induced lipodystrophy. Due to the diversion of amino-acids to glucose, they are considered anti-anabolic, and long term therapy can cause muscle wasting.[24]
Endocrine: By increasing the production of glucose from amino-acid breakdown and opposing the action of insulin, corticosteroids can cause hyperglycemia,[25] insulin resistance and diabetes mellitus.[26]
Skeletal: Steroid-induced osteoporosis may be a side-effect of long-term corticosteroid use.[27][28][29] Use of inhaled corticosteroids among children with asthma may result in decreased height.[30]
Gastro-intestinal: While cases of colitis have been reported, corticosteroids are often prescribed when the colitis, although due to suppression of the immune response to pathogens, should be considered only after ruling out infection or microbe/fungal overgrowth in the gastrointestinal tract. While the evidence for corticosteroids causing peptic ulceration is relatively poor except for high doses taken for over a month,[31] the majority of doctors as of 2010 still believe this is the case, and would consider protective prophylactic measures.[32]
Eyes: chronic use may predispose to cataract and glaucoma.
Vulnerability to infection: By suppressing immune reactions (which is one of the main reasons for their use in allergies), steroids may cause infections to flare up, notably candidiasis.[33]
Pregnancy: Corticosteroids have a low but significant teratogenic effect, causing a few birth defects per 1,000 pregnant women treated. Corticosteroids are therefore contraindicated in pregnancy.[34]
Habituation: Topical steroid addiction (TSA) or red burning skin has been reported in long-term users of topical steroids (users who applied topical steroids to their skin over a period of weeks, months, or years).[35][36] TSA is characterised by uncontrollable, spreading dermatitis and worsening skin inflammation which requires a stronger topical steroid to get the same result as the first prescription. When topical steroid medication is lost, the skin experiences redness, burning, itching, hot skin, swelling, and/or oozing for a length of time. This is also called 'red skin syndrome' or 'topical steroid withdrawal' (TSW). After the withdrawal period is over the atopic dermatitis can cease or is less severe than it was before.[37]
In children the short term use of steroids by mouth increases the risk of vomiting, behavioral changes, and sleeping problems.
52
AKI definition
Creatinine clearance is above 50% of the baseline
53
What is amyloidosis?
Amyloidosis (am-uh-loi-DO-sis) is a rare disease that occurs when an abnormal protein, called amyloid, builds up in your organs and interferes with their normal function.
Amyloid isn't normally found in the body, but it can be formed from several different types of protein. Organs that may be affected include the heart, kidneys, liver, spleen, nervous system and digestive tract.
54
Sx of amyloidosis
Signs and symptoms of amyloidosis may include:
Swelling of your ankles and legs
Severe fatigue and weakness
Shortness of breath with minimal exertion
Unable to lie flat in bed due to shortness of breath
Numbness, tingling or pain in your hands or feet, especially pain in your wrist (carpal tunnel syndrome)
Diarrhea, possibly with blood, or constipation
Unintentional weight loss of more than 10 pounds (4.5 kilograms)
An enlarged tongue, which sometimes looks rippled around its edge
Skin changes, such as thickening or easy bruising, and purplish patches around the eyes
An irregular heartbeat
Difficulty swallowing.
55
Causes of amyloidosis
Causes
There are many different types of amyloidosis. Some varieties are hereditary. Others are caused by outside factors, such as inflammatory diseases or long-term dialysis. Many types affect multiple organs, while others affect only one part of the body.
Subtypes of amyloidosis include:
```
AL amyloidosis (immunoglobulin light chain amyloidosis). The most common type of amyloidosis in developed countries, AL amyloidosis is also called primary amyloidosis. It usually affects the heart, kidneys, liver and nerves.
AA amyloidosis. Also known as secondary amyloidosis, this variety is usually triggered by an inflammatory disease, such as rheumatoid arthritis. Improved treatments for severe inflammatory conditions have resulted in a sharp decline in the number of cases of AA amyloidosis in developed countries. It most commonly affects the kidneys, liver and spleen.
Hereditary amyloidosis (familial amyloidosis). This inherited disorder often affects the nerves, heart and kidneys. It most commonly happens when a protein made by your liver is abnormal. This protein is called transthyretin (TTR).
Wild-type amyloidosis. This variety of amyloidosis occurs when the TTR protein made by the liver is normal but produces amyloid for unknown reasons. Formerly known as senile systemic amyloidosis, wild-type amyloidosis tends to affect men over age 70 and typically targets the heart. It can also cause carpal tunnel syndrome.
Localized amyloidosis. This type of amyloidosis often has a better prognosis than the varieties that affect multiple organ systems. Typical sites for localized amyloidosis include the bladder, skin, throat or lungs. Correct diagnosis is important so that treatments that affect the entire body can be avoided
```
56
RFs of amyloidosis
Factors that increase your risk of amyloidosis include:
Age. Most people diagnosed with amyloidosis are between ages 60 and 70, although earlier onset occurs.
Sex. Amyloidosis occurs more commonly in men.
Other diseases. Having a chronic infectious or inflammatory disease increases your risk of AA amyloidosis.
Family history. Some types of amyloidosis are hereditary.
Kidney dialysis. Dialysis can't always remove large proteins from the blood. If you're on dialysis, abnormal proteins can build up in your blood and eventually be deposited in tissue. This condition is less common with more modern dialysis techniques.
Race. People of African descent appear to be at higher risk of carrying a genetic mutation associated with a type of amyloidosis that can harm the heart
57
Cx of amyloidosis
Complications
The potential complications of amyloidosis depend on which organs the amyloid deposits affect. Amyloidosis can seriously damage your:
Heart. Amyloid reduces your heart's ability to fill with blood between heartbeats. Less blood is pumped with each beat, and you may experience shortness of breath. If amyloidosis affects your heart's electrical system, your heart rhythm may be disturbed. Amyloid-related heart problems can become life-threatening.
Kidneys. Amyloid can harm the kidneys' filtering system, causing protein to leak from your blood into your urine. The kidneys' ability to remove waste products from your body is lowered, which may eventually lead to kidney failure and the need for dialysis.
Nervous system. You may experience pain, numbness or tingling of your fingers or numbness, lack of feeling or a burning sensation in your toes or the soles of your feet. If amyloid affects the nerves that control your bowel function, you may experience periods of alternating constipation and diarrhea. If it affects the nerves that control blood pressure, you may feel faint after standing up too quickly
58
Stages of CKD
Your eGFR results is given as a stage from 1 of 5:
```
stage 1 (G1) – a normal eGFR above 90ml/min, but other tests have detected signs of kidney damage
stage 2 (G2) – a slightly reduced eGFR of 60 to 89ml/min, with other signs of kidney damage
stage 3a (G3a) – an eGFR of 45 to 59ml/min
stage 3b (G3b) – an eGFR of 30 to 44ml/min
stage 4 (G4) – an eGFR of 15 to 29ml/min
stage 5 (G5) – an eGFR below 15ml/min, meaning the kidneys have lost almost all of their function.
```
59
Class of drug Valcade is in?
Proteasome inhibitor
60
Adverse effects of Velcade
Gastro-intestinal (GI) effects and asthenia are the most common adverse events.[7] Bortezomib is associated with peripheral neuropathy in 30% of people resulting in pain. This can be worse in people with pre-existing neuropathy. In addition, myelosuppression causing neutropenia and thrombocytopenia can also occur and be dose-limiting. However, these side effects are usually mild relative to bone marrow transplantation and other treatment options for people with advanced disease. Bortezomib is associated with a high rate of shingles,[8] although prophylactic acyclovir can reduce the risk of this.[9]
Ocular side effects such as chalazion or hordeolum (stye) may be more common in women and have led to discontinuation of treatment.[10] Acute interstitial nephritis has also been reported
61
What do B-lymphocytes mature into?
Plasma cells -> antibodies
62
What are antibodies made up of?
Light chains and heavy chains
63
Which part of antibodies are produced in excess usually and how its the excess removed?
Light chains usually synthesised in excess
| Normally, cleared by the kidney
64
What are Bence-Jones proteins?
Normally excess light chains [<10mg] cleared by the kidneys, however if there's excess proteins [usually over 10mg] then they are usually called Bence-Jones proteins
65
Why is electrophoresis used and not urine dipstick to detect light chains?
Urine dipstick can only detect proteins like albumin and not sensitive enough for urine
66
What are the heavy and light chains?
Heavy chains:
- G [75-80%]
- A [10-15%]
- M [5-10%]
- E
- D
Light chains
- k
- y
e.g. IgGk
67
What does electrophoresis do?
Separates the components of plasma proteins
68
What do proteins move based on in electrophoresis?
Their charge and mass
69
What is on the graph of a electrophoresis?
Albumin, alpha1, alpha2, beta, gamma [the last four are all globulins]
70
What is the most abundant protein int he blood?
Albumin
71
What could cause the spike in M protein?
Could be M, A, G, E, D
| Could be kappa or lambda
72
What is the most common type of gammopathy?
IgG
73
Why are patients with monoclonal gammoapthy immunosuppressed?
Only one cell dramatic rise in protein -> all other plasma cells are suppressed
Why patients with it are immunologically suppressed
74
How are light chains usually secreted in monoclonal gammopathies?
Secreted in urine in the form of Bence-Jones protein
75
Classification of monoclonal gammopathies
- MGUS
- MM
- light chain amyloidosis
- solitary plasmacytoma
- Waldenstrom macroglobulinemia
- heavy chain disease
76
What tests would be ordered in a 70 y/o patient with bone pain, raised calcium and creatinine?
SPEP + immunofixation
SPEP would show a raised monoclonal gammopathy
Immunofixation would show the type of raised protein
77
Why is their increase risk of bacterial infections in MM
problem with plasma cells in MM -> plasma cells from B-lymphocytes -> decrease in humeral immunity -> increased risk of infection from S.aureus/E.coli etc., but not viruses [normal T-cell functiom]
78
What can produce an M component?
| What are they called?
- intact immunoglobulin [any subclass from IgG to IgE]
- fragments of heavy or light chains
These proteins are called paraproteins; why monoclonal gammopathies are known as "paraproteinemias"
79
Epidemiology of MM
10% of haematological malignancies
More common in African Americans
MM is very rare before 40 y/
Medain age onset is 70 y/o
80
What increases the risk of developing MM?
Benzene [petrolium products]/ pesticide exposure
81
Which is the most common subtype of MM?
IgGl, followed by IgA and pure light chain myeloma [kappa and lambda]
82
Definition of M protein MM
Serum M protein over 3 g/dL
83
Clinical picture for MM skeletal system
Skeletal system: disseminated bone disease [punched out lytic bone lesions], pathological fractures, hypercalcaemia
84
Hematology in MM clinical features
Haematology: anaemia [normyctic normochromic with MCV 80-100], rouleaux formation with increased ESR, increased bleeding time as immunoglobulins everywhere on platelets and means why can't aggregate
85
Why does dialysis correct the bleeding time in MM?
Increase in bleeding time due to immunoglobulins covering everywhere, M protein interacting with clotting factors 1,2,5,7,8
Amyloidosis damages the endothelium
86
Neurology in MM
Radiculopathy
- vertebral fractures and compressions will impinge nerve roots
- oncological emergency; loss of bowel and bladder control
Neuropathy
- carpal tunnel syndrome etc., because of amyloid depooisitoin infiltrate soft tissue around the median nerve at the flexor retinaculum
Lethargy, confusion and weakness due to hypercalcaemia
SOB, headache, fatigue due to hyperviscosity syndrome [M protein is everywhere]
87
Kidney clinical picture in MM
Renal failure chronic
- increased calcium
- amyloid deposition
- tubular obstruction by Bence-Jones protein
- direct toxicity of paraproteins
- use of NSAIDs for pain
Different renal presentations
- proteinaceous tubular casts [BJ, immunoglobulins, albumin, Tamm..Hors fall protein]
- nephrocalcinosis: hypercalcaemia
- metastatic disease of the interstitium
- 1ry amyloidosis AL fibrillar patient derived from immunoglobulin LC
- pyelonephritis [bacterial] because B-lymphocytes are crazy, increase calcium leads to dehydration, renal stones, increased risk of infection
- proteinuria: BJ protein is so abundant -> exceeds the ability of the tubule to resorb
88
Recurrent infection in MM
Crazy B-lymphocyte -> decrease humeral immunity
89
Signs of hyperviscioity syndrome i MM
SOB, headache, fatigue, visual disturbance etc.
90
local tumour Sx in MM
produce local Sx based on location
91
What evidence may there by of end-organ damage
C - calcium elevation of over 10mg/dL
R - renal insufficiency
A - anaemia [normocytic and normchromic]
B - bone lesions
92
Cx of MM
1. RTA: BJ damages the tubules "PCT" -> type 2 proximal RTA, type 1 distal RTA. Kidney cannot produce an acidic concentrated urine
2. Proteinuria without hypertension
3. MM -> ALL
4. When there is more protein, there is less water in the same volume of plasma therefore in MM -> more M protein -> less water -> dehydration -> renal failure
The kidney without pressure the kidney is ruined!
5. Leurkoerythroblastosis: the presence of immature [WBCs/RBCs] in the peripheral blood
93
What can hypercalcaemia be due to?
increased production go PTHrP OR
| Lytic skeletal metastases [MM or breast cancer]
94
characteristics of kidney damage in MM
- glomerular function is nearly normal -> no increase in albuminuria -> urine dipstick: ok
- tubules are destroyed by gammaglobulins -> increase globulin in urine -> abnormal urine electrophoresis
95
How can cryoglobulinemia lead to Raynaud's?
Cryoglobulinemia is associated with HCV, type 1 MPGN, MM -> if the M component forms cryoglobulin -> Raynaud's phenomen
96
Metastitic vs dystrophic calcification in MM
Metastitic:
- disease in increase calcium -> Sx of calcium deposits in normal tissue
Dystrophic:
- areas of necrosis
- think destruction granuloma
- doesn't care about serum calcium level
97
Most common Sx in MM
bone pain
98
2nd most common clinical problem is?
Bacterial infection
99
most common infection in MM
UTI and pneumonia
100
Most common infectious pathogens in MM?
Staph, strep, ecoli, kelbsiella
101
Plasma level of alkaline phosphate in MM is usually?
normal
102
Anion gap in MM is usually?
Low anion gap
