AC1 guided learning Flashcards
(122 cards)
1
Q
What are the contents of the normal U&E test?
A
- Sodium (Na)
- Potassium (K+)
- Creatinine (Cr)
- Urea (U)
- eGFR
2
Q
What additional tests to U&E are commonly requested which also come under the umbrella of biochemistry?
A
This is not a complete list, but common biochemical tests are: - Uric acid - Calcium/bone profile - Hormone panels - Blood glucose monitoring tests Creatinine Kinase
3
Q
what systems are investigated through U&Es?
A
- Renal damage such as Acute Kidney Injury
- Bone turn over through calcium release
- Endocrine conditions which can cause electrolyte imbalances e.g. Addison’s
4
Q
What can cause hyperkalaemia?
A
Tissue damage Acute kidney injury Haemolysis Addison’s disease Drugs
5
Q
what can cause hypokalaemia?
A
High levels of insulin
Diarrhoea
Conns syndrome
Poor diet
6
Q
what can cause hyponatraemia?
A
Water intoxication
Addison’s disease
Nephrotic syndrome
7
Q
what can cause hypernatraemia?
A
Dehydration
Perspiration
High salt diet
Diabetes inspidous
8
Q
what can cause raised urea?
A
AKI
Dehydration
CKD
9
Q
what can cause raised creatine kinase?
A
Strenous exercise
Muscle death
Crush injuries
Sustained muscle contraction –e.g. tetany
10
Q
what is creatine kinase?
A
CK is an enzyme responsible for utilization of ATP, particularly in muscles, producing photocreatine as an energy store for the muscle
11
Q
what can cause raised creatinine?
A
Renal impairment,
Hypotension,
dehydration
Note creatinine is both generated and excreted by the kidneys
12
Q
If a patient is found to have mildly raised potassium, what action should be taken?
A
- Review for possible medications associated with hyperkalaemia, and consider continued prescription
- Repeat blood test – in a serum sample with only mildly raised potassium, the likeliest cause is going to be complications in phlebotomy, e.g. tourniquet on too long, excess shaking in transit damaging blood cells, tube heating
13
Q
Assuming hyperkalaemia is substantiated, what three physiological mechanisms give rise to hyperkalaemia? Give examples of each.
A
- Reduced excretion o Renal failure/impaired renal function o Drugs o Addison’s disease - Increased intake o Normally only issues with parenteral or IV fluids excess as it would be expected a healthy patient would be able to increase excretion - Excessive production – main source is break down od cells: o Haemolysis o Tumour lysis o Rhabdomyolysis o Drugs o Blood transfusion
14
Q
Which common medications can cause hyperkalaemia?
A
- Spironolactone
- ACEi
- ARBs
- Omeprazole
- NSAIDs
15
Q
What is a pneumothorax?
A
A pneumothorax is the presence of air in the intra-pleural space.
The intra-pleural pressure will increase (become less negative) and will eventually approach zero or even become positive.
Lack of negative intra-pleural pressure means the lungs collapse (remember their natural tendency is to collapse but they are held open by the negative intra-pleural pressure!) and also means that the chest wall tends to spring out.
16
Q
What are the common causes of pneumothorax?
A
- spontaneous and idiopathic
- spontaneous and secondary to an underlying lung disease e.g. COPD, TB, asthma, lung abscess, cystic lung disease, lung cancer
- traumatic i.e. following injury to the chest wall.
17
Q
What are the common symptoms associated with pneumothorax?
A
- sudden onset, unilateral chest pain, which is often pleuritic
- acute dyspnoea.
18
Q
Signs of pneumothorax?
A
- reduced chest expansion of the affected side
- resonance or hyper-resonance on percussion over affected side
- absent breath sounds
additional for tension:
- deviation of trachea
- tachycardia
- hypotension
19
Q
symptoms? of pulmonary fibrosis?
clinical signs of pulmonary fibrosis?
changes on CXR?
spirometry pattern?
A
progressive SOB
Digital clubbing can be seen and late, often fine, inspiratory crackles can be heard on auscultation of the lungs.
The disease is one of the interstitium and so you evidence of involvement of the supporting tissue of the lung parenchyma resulting in fine or coarse reticular opacities or small nodules.
restrictive pattern, FEV1/FVC normal or increased (as both reduced)
20
Q
Joyce, a 57 year old woman who works as a cleaning lady. She has increasing shortness of breath which is starting to affect her ability to work and look after her grandchildren. Joyce is an infrequent attender at the General Practice, but often uses the walk in centre attached to the hospital where she works. The GP notes that the patient has been attending the walk in centre with ‘chest infections’ about every four months for a couple of years.
Joyce describes a cough, present throughout the year which is productive of sputum, two to three tablespoons a day. The sputum is often white, but can be yellow-green and this tends to be when she goes to the walk in centre.
DDx??
A
• Bronchiectasis • COPD • Asthma • GORD • Alpha 1 antitrypsin • Lung abscess - malignancy
preferred Dx is Bronchiectasis- this sputum production is every day (making COPD less likely) and is copious. There is no wheeze and no evidence of heart burn or waterbrash. Alpha-1-antitrypsin would normally have presented earlier and also affect the liver.
21
Q
Ix for bronchiectasis?
A
Sputum culture: to look for micro-organisms present and their sensitivity to antibiotics
Blood tests to confirm infection: Full blood count and CRP/ESR
High-resolution CT (HRCT) scanning is the criterion standard for the diagnosis of bronchiectasis
22
Q
Changes on CT for bronchiectasis?
A
- Cylindrical bronchiectasis has parallel tram track lines, or it may have a signet-ring appearance composed of a dilated bronchus cut in a horizontal section with an adjacent pulmonary artery representing the stone
- The diameter of the bronchus lumen is normally 1-1.5 times that of the adjacent vessel; a diameter greater than 1.5 times that of the adjacent vessel is suggestive of bronchiectasis
- Varicose bronchiectasis has irregular or beaded bronchi, with alternating areas of dilatation and constriction
- Cystic bronchiectasis has large cystic spaces and a honeycomb appearance; this contrasts with the blebs of emphysema, which have thinner walls and are not accompanied by proximal airway abnormalities ‘
23
Q
• What are the organs of the haematolymphoid system?
A
o Thymus (organ) o Bone Marrow o Lymph nodes (organ) o Spleen (organ) o Mucosa associated lymphoid tissue
24
Q
What are four major functions of the spleen?
A
o Production of an immunological response against blood borne antigens
o Removal of particulate matter and aged or defective blood cells from the circulation
o Recycling iron back to the marrow
o Extra-medullary haematopoiesis in the fetus and during certain bone marrow diseases
The spleen essentially performs the same function for blood that lymph nodes perform for the lymph
25
What is lymph?
. The lymph is formed by the excess fluid that is left in tissues due to the differences in hydrostatic and oncotic pressures from the arterial to venous ends of a capillary bed. Lymph will be greatest where the vessels are leaky e.g. during inflammation. Lymph will also contain dead cells, fragments of degraded tissue and any antigens that have broken through the physical barrier of the skin/mucosa.
26
What are antigen presenting cells?
o Non-professional (all cells nucleated cells of the body)- express MHC Class 1. Viral antigens of cancer antigens would be expressed by these cells in associated with the MHC Class 1 and would invoke a response by cytotoxic T cells.
o Professional APC (e.g. dendritic cells, macrophages, Langerhans cells) take in external antigen, process it and present it bound to MHC Class II receptors. Class II+ antigen promote T helper cell response, which then activate B cells.
27
What are B cells?
o B cells are derived from the bone marrow. Stimulated B cells will mature into plasma cells (antibody factories). The antibodies will be of one of five classes (Ig- G, A, D, M and E). The Ig will then be secreted into the circulation (a proportion will remain bound to B cell membrane to act as the B-Cell receptor). Once activated B cells will mitotically divide producing a mixture of plasma cells and memory B cells (capable of mounting a secondary immune response: more rapid, greater magnitude and produces IgG that the primary immune reponse)
28
What are T cells?
T cells o have effector and regulatory functions. T cells migrate from the bone marrow to the thymus where they develop into mature T cells (or undergo apoptosis if they are self-reactive). T cells then move into the secondary lymphoid organs e.g. lymph nodes and MALT, but are constantly circulating round. The major classes of T cells are:
♣ T helper cells- help other cells to perform their effector functions by secreting interleukins:
• TH1- promote a cell mediated reaction
• TH2- promote humoral immunity
• TH17- acute inflammation
♣ T cytotoxic cells- kill viral and cancer cells. Require help from TH cells to become active.
29
where are B cells and T cells in a lymph node?
B cells are in the follicles
Plasma cells are in the medulla
T cells are in the paracortex
30
What are the characteristic microanatomical features of the spleen?
♣ Red pulp: interconnected sinuses that are the tributaries of the splenic vein. The blood cells enter the parenchyma from capillaries, squeeze through the walls of the sinuses and drain out via the splenic vein (open circulation)
♣ White pulp (20% of mass): periarteriolar lymphoid sheaths consistently mainly of TH1 cells. There is a prominent marginal zone of medium cells.
31
What is a retrovirus?
A retrovirus is an RNA virus that replicates and produces its viral RNA from a DNA copy that is spliced into the host cell DNA. This requires the enzyme reverse transcriptase (transcription is the process of making RNA from DNA).
32
How is HIV transmitted?
Virus is found in blood, semen, cervical and vaginal secretions (it may also be in other body fluids, but there is no evidence linking these to transmission events). Transmission is most likely when the virus load (level) is highest.
The major modes of transmission are: unprotected penetrative sexual intercourse (>=90% of transmissions) (particularly high for recipients of anal sex), via infected blood and blood products (including sharing contaminated needles) and vertical transmission
33
What does vertical transmission mean? How likely is it?
Vertical transmission is the passing of the disease from mother to child. Most of this occurs in late pregnancy or during delivery. The likelihood depends on maternal viral load; if the mother’s HIV is suppressed, then transmission is <2%. Vertical transmission is more likely if the mother has primary HIV(see below), late stage HIV, other sexually-transmitted disease, or breast-feeds her infant.
34
How does the HIV virus cause disease?
HIV has specific tropism for CD4 positive T lymphocytes and also infects monocyte-macrophage lineage cells This infection and then destruction of immune system cells is responsible for the clinical manifestations.
Viral replication, killing of infected cells by cytotoxic T lymphocytes and natural killer cells and increased apoptosis in infected and uninfected CD4 T cells all leads to decline in CD4 positive T lymphocytes.
35
What are the stages of HIV infection?
Primary HIV infection, often called seroconversion, happens 10-30 days after exposure. It may be symptomatic with some (up to 70% of patients) or all (only 5-10% of patients) of: fever, pharyngitis, flu-like symptoms, generalized lymphadenopathy and maculopapular rash.
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The infection then enters the asymptomatic phase, which may last up to 10 years or possible more, the virus is replicating in this time but not causing clinically overt disease. Sometimes persistent, generalized lymphadenopathy is present during this ‘asymptomatic” stage.
The development of clinically overt symptoms signals the entry to the category of AIDS-related illness, or AIDS.
The CDC (Communicable Disease Center) staging of HIV disease is different, using both CD4 T cell count (see question 6) and presence or absence of AIDS-defining condition (see question 8). The WHO stage is slightly different again. These are both surveillance definitions rather than ones used for patient care.
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36
what are some aids-defining illnesses?
Candidiasis of bronchi, trachea or lungs. Lymphoma, Burkitt's (or equivalent term).
Candidiasis, oesophageal.
Lymphoma, immunoblastic (or equivalent term).
Cervical carcinoma, invasive. Lymphoma, primary, of brain.
Coccidioidomycosis, disseminated or extrapulmonary.
Mycobacterium avium complex (MAC) or M. kansasii, disseminated or extrapulmonary.
Cryptococcosis, extrapulmonary. Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary).
Cryptosporidiosis, chronic intestinal (>1 month's duration).
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary.
Cytomegalovirus (CMV) disease (other than liver, spleen or nodes).
Pneumocystis jirovecii pneumonia.
CMV retinitis (with loss of vision). Pneumonia, recurrent.
Encephalopathy, HIV-related. Progressive multifocal leukoencephalopathy.
Herpes simplex: chronic ulcer(s) (>1 month's duration); or bronchitis, pneumonitis or oesophagitis.
37
How do we diagnose HIV?
HIV antigen testing (quick)
Antibody to HIV detection (After 1-2 months)
Older HIV tests relied on detection of antibody to HIV, using ELISA. However, the seroconversion to antibody positivity takes 1-2 months on average, leading to the “seroconversion window” when diagnosis could be missed because no antibody is present.
The testing strategy requires 1 screening test followed by 2 confirmatory tests on the same sample using different targets, plus a 2nd specimen from the patient.
Newer tests and testing strategies detect HIV antigen, usually the p24 envelope protein, they are therefore positive earlier than the antibody based tests
HIV RNA can also be detected in blood using PCR. This can be quantitative and is used for monitoring viral loads.
38
DDx for a maculopapular rash in a child?
Viral exanthem– rubella, measles, scarlet fever, roseola infantum, erythema infectiosum/fifth disease
Drug eruption
Allergic reaction
39
What the white spots on the tongue pathognomic in measles called?
Koplik spots. They are pathognomic for measles and occur 1-2 days before the rash onset. They are usually located near the lower pre-molars. The spots are small greyish-white surrounded by an erythematous base.
40
What is the normal heart rate for a 4 year old?
110-160 bpm
41
What are the Sx of measles?
- m/p rash, starting on neck and face and spreading to trunk and limbs.
- fever
- prodome: malaise, rhinorrhea, conjunctivitis
- koplik spots
42
What protection does the MMR provide against measles?
90%
43
How is measles spread?
airborne or droplet transmission
44
how long is incubation period of measles?
8-14 days
45
how long is a patient with measles infectious?
from start of prodromal symptoms to 4 days after rash onset
HCPs in contact with infectious patient with evidence of protection can continue to work normally, but HCPS without MMR should be excluded from work from 5th day after exposure until 21 days after exposure (unless they are found to be IgG positive)
46
how is measles managed?
supportive treatment - hydration and anti-pyretics
advice verbally and written to keep patient away from susceptible individuals until 5 days after rash onset, and advise on deterioration and complications
send saliva smple to lab to confirm diagnosis, and notify
47
what are the complications of measles?
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otitis media 8%
pneumonia 3%
diarrhoea 8%
convulsions 0.5%
encephalitis 0.1%
death 0.02
```
48
What endocrine response would you expect to fluid deprivation ?
1) Hypothalamic osmoreceptors notice a change in osmolality (more concentrated) and respond by releasing antidiuretic hormone.
Activation of the renin-angiotensin-aldosterone system in response to drop in pressure
49
What (briefly) does a water deprivation test involve?
A patient is admitted to a ward and deprived of water. The patient’s weight, serum osmolality, urine osmolality and vital signs are monitored. In a normal person the urine would concentrate in response to the lack of water intake.
If the urine fails to concentrate, the patient is then administered synthetic antidiuretic hormone (DDAVP) and the response (i.e. urine osmolality) is monitored.
50
How can a GP initally treat thyrotoxicosis pharmacologically?
Carbimazole – anti-thyroid drug, would be the most appropriate first line treatment.
Propranolol – used to manage symptoms whilst waiting for carbimazole to work.
Long term treatment options include radioactive iodine or thyroid surgery, however that decision will be made after full evaluation of the thyroid nodule (i.e. surgery may be indicated if there is a suspicion of thyroid cancer).
51
What are the types of thyroid cancer?
Follicular & papillary.
Anaplastic (fast growing and invariably fatal)
Medullary (from C-cells)
52
What are the two most common differentials in hypercalcaemia?
Malignancy and primary hyperparathyroidism.
53
What is your differential diagnosis for a raised PTH?
Primary hyperparathyroidism – inappropriately high (or normal) PTH in the presence of hypercalcaemia.
Secondary hyperparathyroidism – Usually with normal or low calcium, seen in vitamin d deficiency and renal failure (poor hydroxylation of vitamin D).
Tertiary hyperparathyroidism – typically seen in chronic renal failure after a long history of secondary hyperparathyroidism where PTH secretion becomes calcium independent.
54
If a pituitary tumour is suspected, what investigations should a GP do?
Baseline pituitary function (all at 9am):
Cortisol, testosterone, LH, FSH, Prolactin, TSH and free T4
Measurement of ACTH and GH are not appropriate outside of stimulation tests.
9am cortisol may need further clarification with synacthen test.
TSH alone will not be helpful, as you need to see if it is “appropriate” to the fT4.
IGF-1 can be measured but will be of limited clinical relevance at this stage.
MRI pituitary with contrast.
55
How are prolactinomas managed?
Cabergoline – a dopamine receptor agonist.
Prolactinomas are the only pituitary macroadenomas which can be treated primarily medically. They often shrink dramatically in response to cabergoline. Repeat MRI and prolactin levels will be done to monitor response. Testosterone production should return once the prolactin levels are normalised.
56
What are the contents of the normal LFT panel?
Common LFT panel contents:
- Bilirubin
- Alkaline phosphatase (ALP)
- Alanine transaminase (ALT)
- Serum Albumin
Other tests that can be seen in “liver panels” but are requested specifically:
- Aspartate transaminase (AST) – often not performed unless specifically requested.
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additionally:
Clotting tests e.g. Prothrombin time (PT), APTT
Gamma glutamyl transferase (GGT),
Iron studies
Hepatitis serology
Auto-antibodies
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57
what does raised ALP mean?
- Raised in damage to bile ducts, e.g. obstruction, cholestasis, infiltrative liver disease
- Release from bone turn over, e.g. fracture healing, bony metastasis, Paget’s disease
Highest in third trimester of pregnancy
58
what does raised gamma glutamyl transterase mean?
damage to liver ducts - raised in chronic alcohol abuse
59
what does raised ALT mean?
Damage to hepatocytes: hepatitis, chronic liver disease, drug induced liver damage.
Small release from heart, muscles, kidneys, pancreas
60
what does low albumin mean?
Marker of synthetic function of the liver. Reduced in sepsis, chronic disease states and cirrhosis
61
what does raised PTT mean
A measure of the extrinsic pathway of coagulation, the main rate limiting step is availability of Factor VII, which is produced by the liver, hence increased PTT is an indirect measure of liver function
62
SSx and features of acute liver disease?
* Pruritus
* Jaundice
* Odema
* Abdominal pain
* Fever
* Changes to urine and stool
* Drug and sexual hx
* Foreign travel
* Recent food poisoning – Hep A
* Fatigue
* Fhx
* Previous Hx - gallstones
63
Hx to ask about in chronic liver disease?
* Weight changes – note can be gains as well as losses
* Anorexia
* Jaundice
* Changes to urine and stool
* Alcohol consumption
* Gynaecomastia
* Easy bruising
* Arthralgias
* Fhx
* Mental state changes
* Haematemesis
* Previous hospital admissions
64
List infectious causes of hepatitis?
- Hep A,B,C,D,E
- EBV (glandular fever)
- amoebic/parasitic
- CMV
65
Urine, Faeces, Type of hyperbilirubinaemia in Pre-hepatic, Hepatic and Post-hepatic
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Pre-Hepatic:
Normal urine
Normal/
darkened faeces
Unconjugated hyperbilirubinaemia
```
Hepatic:
Darker urine
Lighter faeces
Mixed conj/unconj
Post-hepatic:
Dark urine
Light stools
Conjugated hyperbilirubinaemia
66
When does jaundice become clinically apparent?
Jaundice is only clinically apparent (i.e. visible) when bilirubin levels rise >40unol/L.
67
What imaging is used to investigate query pancreatic cancer
CT
68
What drug is used after acute paracetamol overdose, and in what time frame?
within 72 hours
| N-acetyl cysteine
69
What classification system is commonly used to assess liver failure?
Parameters?
Child Pugh classification
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Ascites
Bilirubin
Albumin
PTT/INR
Encephalopathy
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Grades A well compensated
B significant functional compromise
C decompensated (1 year survival 45%)
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70
What are enzyme inducers?
Examples?
a drug, which when taken, increases the metabolic activity of an enzyme, either through activation or upregulation of gene expression - Normally considered to be referring to liver enzymes – This may impact on other medications metabolized through the same pathway, by increasing their breakdown, thus requiring dose adjustments
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Examples:
• Rifampicin
• Carbamazepine
• Tobacco
• isoniazid
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71
What are enzyme inhibitors?
a drug, which when taken, reduces the activity of an enzyme – normally through binding to the enzyme. This MAY have a more significant effect than enzyme inducers, as the broken down of medications through that pathway is slowed, potentially causing overdoses.
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Examples:
• Erythromycin
• Fluoxetine
• Amiodarone
• Fluconazole
• Diltiazem
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72
David Smith is a 56 year old man with known lung cancer. He attends for his routine oncology review. He has been feeling a bit low and has constipation, anorexia and nausea.
What are the differential diagnoses?
Things to consider are: side effects of drugs e.g. chemotherapeutics, paraneoplastic syndrome, depression, cerebral metastasis, or biochemical abnormalities especially hypercalcaemia and hypokalaemia.
Hypercalcaemia- the symptoms are consistent and the patient has a lung cancer, which is a solid tumour which commonly metastasises to bone.
Hypokalaemia- as the patient may not be eating or drinking or could have a lung cancer secreting ectopic hormone (relatively common in lung cancer)
73
How does albumin effect calcium level?
decreased albumin = increased free ionized ca b/c of reduced binding
74
What disease processes lead to primary hyperparathyroidism?
Primary hyperparathyroidism reflects an abnormality in the parathyroid glands. The common causes of primary hyperparathyroidism are a solitary parathyroid adenoma or parathyroid gland hyperplasia.
75
What are the common non-PTH mediated causes of hypercalcaemia?
The common non-PTH related causes of hypercalcaemia are:
• Malignancy e.g. haematopoietic or solid organ with mets or ectopic hormone secretion
• Elevated vitamin D- vitamin D intoxication, sarcoidosis, HIV or other granulomatous disease
• Thyrotoxicosis
• Drug induced e.g. Lithium, thiazide diuretics
76
Imaging for hypercalcaemia?
- ultrasound scan the parathyroid glands
| - bone scan if mets suspected
77
How can malignancy cause hypercalcaemia?
There are three main ways in which malignancy can induce hypercalcaemia:
• osteolytic metastases with local release of cytokines (including osteoclast activating factors)
• Extopic secretion of parathyroid hormone-related protein (PTHrP)
• Ectopic production of active vitamin D
78
How to manage malignancy-related hypercalcaemia?
- admit
- rehydrate
- give bisphosphonates
79
what are the common presenting symptoms of acute leukaemia?
* Anaemia: tiredness, shortness of breath, pallor
* Thrombocytopaenia: easy bleeding and bruising
* Luekopaenia: increase infections
80
What is the major acute complication of chemotherapy in a patient who has an acute leukaemia, with a high proportion of the cells proliferating?
Tumour lysis syndrome, reflecting the breakdown of a high number of cells, which are in the cell cycle.
81
What symptoms does tumour lysis syndrome cause?
what prophylactic is given to reduce risk of tumour lysis syndrome?
The common symptoms are: abdominal pain and distension, urinary symptoms (dysuria, oliguria, flank pain, and hematuria), symptoms of hypocalcaemia (anorexia, vomiting, cramps, seizures, spasms, altered mental status, and tetany), symptoms of hyperkalemia (weakness and paralysis), fluid overload, lethargy, oedema, heart failure, dysrhythmias, sudden death.
ALLOPURINOL
82
what is the MOA of allopurinol?
Allopurinol is a competitive xanthine oxidase inhibitor that reduces the amount of uric acid produced by inhibiting the conversion of hypoxanthine to xanthine and xanthine to uric acid. Reduced uric acid secretion leads to an increase in urinary excretion of hypoxanthine.
83
What are the three most common neoplasms associated with cerebral metastases?
Breast cancer, lung cancer and bowel/GU cancer
84
A patient with acute lymphoblastic leukaemia presents with resp failure and papilloedema: what causes this?
hyperleukocytosis i.e. a very high white cell count
85
Mary Chase is a 54 year old woman who has metastatic breast cancer and is receiving palliative care in the community. Mary is brought into the emergency department with a severe headache, nausea and vomiting.
What is the differential diagnosis?
side effects of drugs e.g. chemotherapeutics
paraneoplastic syndrome
cerebral metastasis
infection
biochemical abnormalities especially hypercalcaemia and hypokalaemia.
86
what imaging to confirm cerebral metastasis?
CT
87
What is the normal intra-cranial pressure?
The normal opening pressure of the CSF is 10-20 cm H2O.
88
How do cerebral metastases cause raised intra-cranial pressure?
Common mechanisms are: presence of a physical space occupying lesion, haemorrhage into or around the met, oedema into or around the met, obstruction of flow of CSF.
89
Herniation is the most significant consequence of raised ICP. What are the major types/sites of herniation of the brain?
Subfalcine herniation
Uncal (transtentorial) herniation
Cerebellar tonsillar herniation.
90
What is an advance care plan?
It is a structured discussion with patients and their families or carers about their wishes and thoughts for the future. Processes which enable individuals to be involved in decisions regarding future care. It is a voluntary process of discussion and review. Identifies a person’s preferences in the context of an anticipated deterioration in their condition
With the individual’s agreement this discussion should be;
¥ documented,
¥ regularly reviewed,
¥ communicated to key persons involved in their care
The process of Advance care planning in the UK includes many elements – essentially helping people approaching the end of their life to describe and clarify
• What they want to happen
• What they don’t want to happen
• Who will speak for them
91
What are the common diseases that affect the prostate? Which areas of the prostate do they normally affect?
* Prostatitis (inflammation)- shows no zonal preference
* Benign prostatic hyperplasia- peri-urethral
* Adenocarcinoma- outer peripheral part of the gland
92
What abnormalities can you detect on DRE of the prostate? What types of disease would each of these changes suggest?
Prostatitis can produce and enlarged tender prostate, which may have boggy consistency on DRE.
Prostatic hyperplasia often produces symmetrical enlargement of the prostate.
A hard, irregular prostate gland is suggestive of prostate cancer, often accompanied by an undetectable median groove/sulcus. Extra-capsular spread of prostate cancer can sometimes be identified by tethering of the rectal mucosa over the prostate.
93
How would you stage the local extent of the prostate cancer? Why this modality?
Prostate MRI is the most accurate way to determine the local extent of the tumour.
MRI scanning is particularly useful at providing highly detailed images of soft tissues.
Patients will also have a trans-rectal ultrasound scan at the time of biopsy which will give an indication of the likely local extent of the tumour.
94
How to vertebral metastasis appear on radiological imaging?
Metastases are either osteoblastic/sclerotic or osteolytic, prostate cancer has a primarily osteosclerotic pheontype. On x-ray the sclerotic lesions will be white. On CT scan sclerotic lesions appear hyperdense and irregular but are unlikely to extend beyond the vertebrae. On MRI the signal intensity of the metastatic deposits will vary according to the degree of mineralisation.
95
What is a neoplasm?
A neoplasm is an abnormal mass of cells, the growth of which exceeds and is uncoordinated with the normal growth control mechanisms of the tissues.
Neoplasms are said to have autonomous growth in that they are resistant to physiological growth control mechanisms. However neoplasms still require a blood supply, nutrition and possibly endocrine stimulation from the host.
96
What differentiates a malignant from a benign neoplasm?
A malignant neoplasm has the ability to invade the surrounding tissues and metastasise. Both benign and malignant tumours can cause death.
97
Morphological features of cancer?
variation between cells
increased size of nucleus (1:1 ratio with cytoplasm)
coarse and clumped chromatin
bizarre shape of nucleus
increased mitotic figures, abnormal form, and can be anywhere
polarity is lost; cell to ECM adhesions disrupted
98
What is dysplasia?
Dysplasia is the disorderly proliferation of cells, but does not represent cancer. There is loss in uniformity of cells and orderly maturation, BUT there is not breech of the basement membrane (most dysplasia involves epithelium)
Dysplasia is often graded as mild, moderate and severe. Dysplasia doesn’t necessarily mean cancer will develop, mild and moderate dysplasia can sometimes be reversed if the stimuli is removed.
99
what is the other term for severe dysplasia in epithelia?
carcinoma in situ
100
Why are many malignant neoplasms firmer than the adjacent tissues e.g. breast cancers and prostate cancers?
As previously stated cancers comprise stroma and parenchyma. As the tumour invades the adjacent connective tissue a very firm form of stroma can form in the neoplasm- desmoplastic stroma, which gives some neoplasms the hard craggy feeling characteristic of cancer on palpation.
101
What is a metastasis?
It is a secondary implant of a neoplasm discontinuous with the primary neoplasm.
102
What are the routes of metastasis?
Transcoloemic (seeding across a body cavity), haematogenous, lymphatic and direct through tissues.
103
What is a sentinel lymph node? What does a negative node mean for the patient?
The sentinel node is the first node in the regional lymphatic group to receive lymph drainage from the neoplastic tissue. A negative node means that no other lymph nodes should be involved and no further lymph gland removal should be necessary. There are few tumours which show consistency in drainage patterns, breast and melanoma being the ones for which this sampling technique is used clinically currently.
104
What are the positive controls on the cell cycle?
The accelerators are growth factors from outside the cell and phosphorylation reactions catalysed by cyclin dependent kinase and cyclin complexes.
105
What are the negative / inhibitory controls on the cell cycle?
The brakes on the cell cycle are applied by cyclin kinase inhibitors and the checkpoints.
106
How do cyclins and cyclin dependent kinases (CDK) work?
Cyclins (as the name suggests) show cyclical variation in levels during the cell cycle. There are several cyclins, which have key roles at different points of the cycle. Cyclins bind to cyclin dependent kinases (CDK)(constant levels throughout cycle but variably active) to form a complex, which activates the CDK. This activated complex phosphorylates target proteins which drive the cell forward through the cell cycle.
107
Where are the key cell cycle checkpoints? What do they look for?
G1/S- DNA damage before DNA is replicated and that the environment is favourable and G2/M checkpoint looking for damaged or unduplicated DNA and checking that the cell is big enough before mitosis.
108
What are the molecular hallmarks of cancer (Hanahan and Weinberg)? There are 10
Replicative immortality
tumour promoting inflammation
activation of invasion and metastasis
induction of angiogenesis
genome instability and mutation
resistance to cell death
dysregulation of cellular energetics
sustained proliferating signalling
evasion of growth suppressors
avoidance of immune destruction.
109
What are the normal genes that promote cell growth? What are their mutated forms called? What are their products called?
The normal growth promoting genes in cells are the proto-oncogenes, and they code for proto-oncoproteins. Mutated forms of the gene in cancer are called oncogenes and they code for oncoproteins.
110
How many alleles of a proto-oncogene need to be mutated for neoplastic transformation? Why?
Mutation of proto-oncogenes behaves in a dominant fashion i.e. a single allele of the gene needs to be mutated to enable neoplastic transformation. This is because its product promotes the cell cycle and so any increase it the level will accelerate the cell cycle.
111
How are growth factor receptors altered to enable self-sufficiency in growth signals?
* Mutated so they are active even without a ligand
* Overexpressed so very low levels of the growth factor (that would normally be insufficient to trigger proliferation) stimulate proliferation e.g. Her2 in breast cancer and EGFR in lung cancers (both treatment targets).
112
How many copies of the TSGs alleles need to be mutated to enable a malignant phenotype to emerge? Why?
Tumour suppressor genes generally require mutations in BOTH alleles to enable a malignant phenotype. This is because any normal allele will continue to produce the regulatory protein at a certain level.
113
Explain the two hit hypothesis of which accounts for the sporadic and familial retinoblastoma tumour formation.
Tumour suppressor genes behave in a recessive manner i.e. both must be mutated for a malignant phenotype to emerge. In familial cases children inherit a single mutant copy and then acquire a somatic mutation leading to loss of heterozygosity of the gene. In sporadic cases two somatic mutations have to occur for both alleles to become mutant. Familial retinoblastoma is an autosomal dominant disease (DO NOT CONFUSE THIS WITH BEHAVIOUR OF TSG mutations).
114
Where in the cell cycle is RB key?
RB is key for the G1/S checkpoint transition
115
molecular basis of RB checkpoint?
The Cyclin E/CDK complex is necessary for DNA synthesis i.e. the S phase of the cell cycle. Active RB binds to E2F and thus blocks transcription of cyclin E.
Cyclin D and CDK4 complex phosphorylates RB (makes it inactive), this releases E2F, which enables cyclin E expression.
116
When in the cell cycle does p53 induce cell cycle arrest?
Late in the G1 phase- remember once into the S phase the cell is committed to mitosis and so if it was any later all the cells in which p53 was activated would have to undergo apoptosis. p53 induces cell cycle arrest by inhibition phosphorylation of RB i.e. the RB remains active.
117
how does familial adenomatous polyposis present?
Patients with FAP have hundreds of adenomatous polyps in their colons and a guarantee that one of these will become malignant.
118
what mutation is present in FAP?
The APC gene is a tumour suppressor gene, a mutant allele is inherited in those with Famililal Adenomatous Polyposis (FAP).
APC regulates intra-cellular expression of β-catenin, which helps to bind E-Cadherin.
β-catenin also signals via the WNT signalling pathway to activate proliferation. Loss of APC means unregulated β-catenin expression and thus unregulated proliferation.
E-Cadherin binds cells together i.e. it is intercellular glue, it is dysregulated in virtually all cancers, loosening intercellular bridges, making the cells more mobile, and the cells lose polarity as they are no longer anchored in place.
119
What is apoptosis?
Apoptosis is programmed cell death, via activation of the caspase cascade.
2 pathways:
The intrinsic cascade relies on a balance between pro-apoptotic molecules and anti-apoptotic molecules and the extrinsic cascade relies on a ligand binding to the death receptor. The process of apoptosis involves the proteolytic cleavage of the caspase enzyme cascade.
120
What structure on the ends of chromosomes limited the number of replications? How does it work? How could this structure be altered to allow for limitless replicative potential?
Telomeres on the end of chromosomes get shorter during each round of proliferation. At a critical point they are identified as double stranded DNA breaks and the cell enters senescence.
Telomerase, an enzyme normally only expressed in utero, can elongate telomeres and thus allow for an infinite number of replications.
121
What growth factor will be the key to vascularisation?
VEGF
Tumours need a vascular supply when they get larger than 1-2mm. The new vessels tend to be leaky, often dilated and have a haphazard pattern of connection
122
What four things does a cell need to do to invade the ECM?
The cell needs to detach from the adjacent cells (reduced expression of E-cadherin)
degrade the ECM (produce proteases eg MMPs)
attach to novel ECM ligands
migrate through the ECM.
