Chemical Biology Flashcards
(246 cards)
1
Q
A 55-year-old woman is warned of future risk of AML given her recent diagnosis of PNH following a spontaneous cerebral venous sinus thrombosis.
A
Paroxysmal nocturnal haemoglobinuria:
- Acquired loss of protective surface GPI markers on RBCs (platelets + neutrophils) →
- complement-mediated lysis → chronic intravascular haemolysis especially at night.
- Morning haemoglobinuria, thrombosis (+Budd- Chiari syndrome – hepatic v thromb).
- Diagnosis: immunophenotype shows altered GPI or Ham’s test (in vitro acid-induced lysis).
- Treatment: iron/folate supplements, prophylactic vaccines/antibiotics. Expensive
- monoclonal antibodies (eculizumab) that prevents complement from binding RBCs
2
Q
A 30-year-old farmer presents to casualty complaining of diarrhoea and painful mouth ulcers. On questioning he admitted accidentally ingesting liquid paraquat
A
Activated charcoal
3
Q
A 26-year-old woman collapses after a massive overdose of atenolol. She remains in cardogenic shock despite initial treatment with IV atropine
A
- Glucagon
- I think this is a slightly tricky question. Glucagon in beta-blocker overdose is to counteract hypoglycaemia secondary to beta- block of glycogenolysis.
- However, it can also have an effect on bradycardia and subsequent cardiogenic shock because glucagon receptors are G-protein coupled receptors that lead to an increase in adenyl cyclase activity and increased intra-cellular cAMP. This bypasses the need for B1-receptor activity to increase cAMP.
4
Q
A pregnant 30-year-old woman is found drowsy in her rented flat. She complains of severe nausea for the last 3 hours. Her carboxyhaemoglobin level is 41%.
A
Hyperbaric Oxygen
5
Q
A 25-year-old man is delirious and hyperpyrexial after taking a pill in a club. He is hyperreflexic and is hyponatraemic.
A
Symptomatic and Supportive treatment
6
Q
Cyanide poisoning
A
Dicobalt edentate
7
Q
pin-point pupils, watery eyes
what it is how you will treat it?
A
Naloxone
8
Q
A
D.
Crigler Najjar syndrome
9
Q
A 35-year-old Afro-Caribbean woman presents with polyuria and polydipsia. She also complains of a dry cough. She has a fasting glucose of 5.8mmol/L and an oral glucose tolerance test value of 6.5mmol/L. She has a corrected calcium of 2.7mmol/L and a PTH of <0.1pmol/L.
A
sarcoidosis
10
Q
Benzodiazepines OD
A
Flumanezil
11
Q
dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision.
arrhythmias
seizures
metabolic acidosis
coma
ECG changes include:
sinus tachycardia
widening of QRS
prolongation of QT interval
A
Management
IV bicarbonate may reduce the risk of seizures and arrhythmias in severe toxicity
arrhythmias: class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation. Class III drugs such as amiodarone should also be avoided as they prolong the QT interval. Response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias
dialysis is ineffective in removing tricyclics
12
Q
Lithium OD
A
Management
- mild-moderate toxicity may respond to volume resuscitation with normal saline
- haemodialysis may be needed in severe toxicity
- sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion
13
Q
Heparin OD
A
Protamine sulphate
14
Q
Beta-Blockers OD
A
Management
- if bradycardic then atropine
- in resistant cases glucagon may be used
15
Q
A 15-year-old girl presents with weight loss, polyuria and polydipsia. Over the last few months she reports feeling increasingly tired and complains of perianal itching. On examination you notice a small perianal abscess. Her fasting glucose is 22.3mmol/L. His corrected calcium is 2.5mmol/L and his PTH is 7.0pmol/L.
A
Diabetes mellitus type 1
16
Q
Ethylene glycol OD
A
- Fomepizole
- Management has changed in recent times
ethanol has been used for many years
works by competing with ethylene glycol for the enzyme alcohol dehydrogenase
this limits the formation of toxic metabolites (e.g. Glycoaldehyde and glycolic acid) which are responsible for the haemodynamic/metabolic features of poisoning
fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol
haemodialysis also has a role in refractory case
17
Q
Methanol poisoning OD
A
Management
- fomepizole or ethanol
- haemodialysis
18
Q
Organophosphate insecticides OD
A
Management
- atropine
- the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit
19
Q
Digoxin OD
A
Digoxin-specific antibody fragments
20
Q
Iron OD
A
Desferrioxamine, a chelating agent
21
Q
Lead OD
A
Dimercaprol, calcium edetate
22
Q
Carbon monoxide OD
A
Management
- 100% oxygen
- hyperbaric oxygen
23
Q
Cyanide OD
A
Hydroxocobalamin; also combination of amyl nitrite, sodium nitrite, and sodium thiosulfate
24
Q
A 56-year-old obese woman presents with polyuria and polydipsia. She complains of tiredness and depression. Her fasting glucose is 4.9mmol/L and her OGTT is 4.5mmol/L. She has a corrected calcium of 2.4mmol/L and a PTH of 7.1mmol/L.
A
Psychogenic polydipsia
Euvolaemia > 20 SIADH, Primary polydipsia, Severe hypothyroidism
25
A 58-year-old Afro-Caribbean gentleman presents with **polyuria**, **polydipsia** and **weight loss**. He has an **oral glucose tolerance** test of **10.1mmol/L.** His corrected calcium is **2.5mmol/L** and his **PTH is 7.0pmol/L.**
**Impaired glucose tolerance**
26
A 35-year-old man presents with hypertension. Blood tests show normal sodium, urea and glucose and a raised potassium. What is the likeliest result of potassium (mmol/l) in a normal person?
4
27
A 70-year-old woman presents in a coma with a long history of **polyuria** and **polydipsia.** Investigations show that her plasma osmolarity is raised. What is the likeliest result of plasma osmolarity (mmol/l) in a normal person?
290
28
Which of the above techniques can be used to test for all classes of drugs of abuse (DOA)?
Immunoassay
29
What sample is required for use with gas chromatography mass spectroscopy?
Blood Sample
30
Colorimetric can be used to test for which drug commonly taken in overdose?
Paracetamol
31
Which of the above techniques can be used to test for benzodiazepines and various antipsychotic drugs?
Liquid chromatography
32
Which of the above techniques can be used to analyse samples of **stool**, **liver** and also **urine**?
**Thin layer chromotography**
33
Which option is the best specimen for assessing long-term drug use?
hair
34
Which drug is found in the most addict related deaths?
Morphine
35
Which option is responsible for the analysis of samples for drugs and poisons?
Toxicology
36
Which option is the best example of a quick, cheap, easy and non-invasive specimen which is likely to be adulterated for forensic drug analysis? Disadvantages include a small window of detection.
Saliva
37
Which drug is not excreted into saliva?
THC
38
An **18 year old female** is brought in to **A&E** from a rave in the early hours of the **morning**. On initial examination she is agitated with a heart rate of **120 bpm**. She is **very sweaty** and has **wide dilated pupils**
Ecstasy
39
## Footnote
A 25 year old male is admitted with hyperventilation. He is sweating and appears nauseous. He says that he has ringing in his ears. Blood gases show that he has mixed acid-base disturbance
**Salicylates**
## Footnote
**Salicylate overdose**
A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate
**Features**
**hyperventilation (centrally stimulates respiration)**
**tinnitus**
lethargy
sweating, pyrexia\*
nausea/vomiting
hyperglycaemia and hypoglycaemia
seizures
coma
**Treatment**
**general (ABC, charcoal)**
**urinary alkalinization with intravenous sodium bicarbonate** - enhances elimination of aspirin in the urine
**haemodialysis**
40
An 80 year old man and his 79 year old wife were brought in after a neighbour found them collapsed in their home. On questioning the neighbour it was found that the couple had not been feeling well for a few weeks and had been complaining of nausea, headaches and dizziness
**c**arbone ***m***onoxide ***p***oisoning
41
A depressed 30 year old woman was brought into A&E after being found by a friend. On examination she appears very drowsy with sinus tachycardia and wide dilated pupils. She has marked reflexes and extensor plantar responses. ECG shows a wide QRS interval
Tricyclic antidepressants
42
Both TCA od's and ecstasy od's can cause wide dilated pupils.
Ecstasy is more likely to lead to agitation and TCA drowsiness.
43
What the effect of **ectasy** on **Na balance** might be?
Also....remember that **ecstasy** may induce **vasopressin secretion** and and SIADH, with hyponatraemia?
44
Varies with posture when sample is taken.
Albumin
45
Increases during pregnancy
ALP
46
**Varies with race**
Creatinie Kinase
47
Most likely to vary with time of sampling
Cortisol
48
Peak and trough levels of this drug should be taken
Gentamicin
49
Symptoms of under-treatment and toxicity may be similar
Digoxin
50
Decreased excretion, increased plasma concentration and increased risk of toxicity may occur when this taken in conjunction with thiazide diuretics
Lithium
51
Is ototoxic and nephrotoxic
Gentamycin
52
Requires regular monitoring of **APTT**
Heparin - unfractionated
53
A **19-year-old** woman admitted to hospital with acute asthma suffered a cardiac arrest after treatment. She was already taking several medications for her respiratory condition. What drug excess is likely to have caused this problem?
Theophylline
54
Lipid soluble drugs require metabolism by the liver in two phases. What is Phase I?
Oxidation by cytochrome P450
55
The effect of which drug can be measured by the surrogate marker HbA1C
Rosiglitazone
56
A 58-year-old man presents to your A&E complaining of chest pain and palpitations. He says he takes several drugs for his 'heart problems' and admits to being diabetic. What drug could be causing his problems?
Digoxin
57
Possible features of DIGOXIN TOXICITY include:
**_confusion_** especially in the elderly
* **_yellow vision_** (xanthopsia), blurred vision and photophobia
* **_anorexia,_** nausea and vomiting and occasionally, diarrhoea
* **_arrhythmia:_** the most common arrhythmias are ventricular extrasystoles, ventricular bigeminy / trigeminy and atrial tachycardia with complete heart block, narrow QRS
58
A man was put into custody after driving under the influence of drugs. On arrest he was reported as acting extremely aggressive and paranoid. He also claimed his heart was racing. One hour later he was found dead. There was suspicion of police brutality.
Cocaine
59
A 24-year-old woman goes to a party where she has some pills. She subsequently becomes feverish and confused. She was found to be hyperthermic and blood results showed a raised urea and creatinine, her myoglobin was also found to be high.
Ecstasy
60
James Pond comes to A&E claiming he’s been poisoned. Minutes later he dies. His skin was brick red and there was a faint odour of almonds.
cyanide
61
Following a death in the family, a young woman is brought into the hospital with confusion. On inspection she appears jaundiced. Her friend reports that she had been vomiting earlier and that she had found an empty medicine bottle in her room.
Paracetamol
62
A man was found collapsed on the floor of his room and his breathing was found to be severely depressed. A urine test was found to be positive for 6-MAM.
Heroin
63
**A liver enzyme** raised after **a myocardial infarction**
**Aspartate transaminase**
64
**An enzyme** markedly raised in **obstructive jaundice** along with direct bilirubin
**Alkaline phosphatase**
65
A **25 year old** male with a history of **tuberculosis** presenting with a plasma osmolality of **205mmol/l,** potassium of **6.3mmol/l** and sodium of **115mmol/l.**
**What other presentations he would have?**
**Addison's disease**
**- posural hypotension**
**- skin pigemntation**
**-lethargy**
**-depression**
66
A 47 year old female presents to her GP with **_severe loin pain = kidney stones?_**
On further questioning the patient complains of a 6 month history **of recurrent fevers** and **vomiting** with more recent generalised weakness and pain in some of her joints. A subsequent blood test shows **hypokalaemia.**
All three types of renal tubular acidosis (RTA) are associated with hyperchloraemic metabolic acidosis (normal anion gap)
**Type 1 RTA (distal)**
* inability to generate acid urine (secrete H+) in distal tubule
* causes hypokalaemia
* complications include nephrocalcinosis and renal stones
* causes include idiopathic, RA, SLE, Sjogren's, amphotericin B toxicity, analgesic nephropathy
Renal tubular acidosis describes tubular abnormalities that give rise to acidosis without affecting GFR.
**Type 1 or distal RTA** results from a failure in H+ excretion from the distal tubule and collecting ducts. **Type 2** is caused by a failure to reabsorb **HCO3** from the **proximal tubule.**
You can see how both of these abnormalities would cause **a metabolic acidosis.** In both cases there is associated **Na wasting --\> secondary hyperaldosteronism --\> K excretion and hypokalaemia.** An excellent runthrough of both types of RTA is provided at
67
What sort of **abnormalities** you would expect in a patient suffering from **the renal failure?**
Renal failure tends to cause HYPERkalaemia as a function of reduced GFR.
68
A junior doctor received a blood report from the pathology lab for a 50 year old male who was recovering from an inguinal hernia repair. The report described the patient as being hyperkalaemic. Most of the porters at the hospital were on strike at the time.
What is **delayed separation?** It is when there is a delay in separating the cells in the blood sample from the serum, so some cells break down and **release potassium**, causing a **falsely high potassium level.** I think it's the same principle as haemolysis causing high potassium eg in the question of the guy with the artificial heart valve.
69
An 82 year old female caught a bad cold on a flight to Heathrow for **a holiday from Indi**a, where she has lived all her life. Six days later she comes into A+E weak, confused with abdominal pain. Blood tests show **a potassium of 6.2mmol/L.**
**Addison's disease: Remember low Na high K+**
70
what is the characteristic of renal tubular acidosis? (3 things)
For the purposes of the **path exam** remember that **RTA** is typically characterised by:
- **acidosis with HYPOkalaemia**
**-** acidosis with _alkaline urine_ and _positive urine anion gap._
- nephrocalcinosis
Type 1 RTA is commoner **than type 2** (typically caused by Fanconi syndrome) and may be **idiopathic** or **secondary.**
A common cause of type 1 RTA is autoimmune, including SLE, which could be causing this ladies joint pain. The severe loin pain is probably due to a renal stone. Another potential cause in this case is chronic pyelonephritis (accounting for 6mo of fevers).
71
What biochemical changes you would expect in diarrhoea?
**Diarrhoea typically results in electrolyte (including K and HCO3)** loss and consequent **HYPOkalaemia** and alkalosis.
If the diarrhoea was severe enough (e.g. cholera) to cause severe dehydration and reduced organ perfusion, **a lactic acidosis** could potentially result.
In general though: diarrhoea --\> hypokalaemia + alkalosis
72
A 65 year old lady presents to **A & E** with her son who describes **decreasing mental function over the last week or so.**
On questioning you discover that she is a smoker with a 40 pack year history and that she **has had a chronic, productive cough for several weeks.** Bloods include **Na=120 (**135 - 145 mmol/l) **,** K=4.5, Cl=85, HC03=22, **_serum osmolality=260_**
**SIADAH. Remember serum osmolality is used to diagnose SIDAH. The normal range for osmalility is 275 - 295 mmol/kg.**
73
A 75 year old lady is recovering from a hip replacement after fracturing her neck of femur. The post-operative period has been uneventful but today you, the F1, notice that her blood results are slightly abnormal: **_Na=126, K=3.2_,** serum _osmolality**=262.**_ You consult your registrar, who tells you not to worry and advises ‘**watchful waiting’**.
**_Iatrogenic_** - volume depletion. Both **NA (125-135)** and **K+** are low **3.5-4.5.**
74
A young drama student attends clinic complaining of **polyuria** and **sleep disturbance.** Her past medical history includes an appendicectomy, a skull fracture, and hayfever. Her biochemistry reveals **Na=148, K=3.6.** She denies excessive fluid intake.
Causes of cranial DI
## Footnote
idiopathic
post head injury
pituitary surgery
craniopharyngiomas
histiocytosis X
DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome)
75
Normovolaemic and hyponatraemic
SIADAH
76
Hypovolaemic with urinary Na+\<10 mmol/L
Vomiting
77
**Raised JVP,** peripheral oedema and urinary **Na+\<10 mmol/L**
cardiac failure
78
**Hypotension** with urinary **Na+\>20 mmol/L**
I.
Diuretic excess
79
**Hypervolaemic** with **urinary** Na+\>20 mmol/L
Chronic renal failure
80
Revise the table provided in the Sodium Handling lecture notes. For more information on SIADH, hyponatraemia or for a discussion of HF vs CKD, see attached file.
81
## Footnote
Why SIADAH is euvolemic?
The patient is euvolaemic because the intravascular volume is affected by sodium not water, which travels across membranes and does not affect your intravascular volume.
Thus in SIADH you have too much water, but this does not make you fluid overloaded. To be fluid overloaded you MUST have too much sodium on board (eg oedema). Karim
82
why would a severe primary hypothyroidism cause hyponatraemia?
The exact mechanism is complicated. However in the absence of adequate thyroxine (and also cortisol), the renal tubules do not clear free water at a normal rate. Thus if you drink some water, the kidneys are slow to clear the free water, and thus hyponatraemia ensues.
83
Why patients with Addisons complain of nocturia?
If a normal person drinks a litre of water, they start to increase their urine output within 20 minutes. If an Addisonian or severely hypothyroid patient drinks a litre of water, they only start increasing urine output an hour later, and this goes on for 24 hours. Thus they complain of nocturia (not polyuria).
84
What is the difference in metbaolite disturbance between the hyperkalemia and hypokalemia?
The raised JVP and **peripheral oedema** occur in both **heart failure** and **renal failure.** However in **heart failure**, the cause of this is a very high (secondary) hyperaldosteronism, as you have spotted.
Thus the urine sodium is very low, because the high aldosterone causes the sodium to be resorbed. **In renal failure**, t**he GFR is reduced**, but also the tubules are less able to exchange sodium for potassium, as they are also damaged in kidney disease.
Although **the aldosterone** might be high, **the renal tubules are damaged,** and are thus less able to respond to the aldosterone. Karim
85
A 46 year old female presents with **confusion** and **complains** of **hallucinations**. On further questioning she reveals that she has been feeling generally tired and weak for the last 8 weeks. During this period she has lost 8 kg in weight. Her past history revealed an episode of **TB 22 years ago**. Her electrolyte results revealed **Sodium 105 mmol/l; potassium 5.5 mmol/l** and **osmolality 220 mmol/l.**
**low Na** (125-135), **high K** (3.5-4.5) **low osmolality** (275-295)
86
A 78 year old male presents with **hypokalaemia**.
He has previously been diagnosed with **congestive heart failure**, which has been controlled with medication.
Serum sodium was **126 mmol/l** and **bicarbonate** was raised.
Use of diuretics
## Footnote
Hypotension with urinary Na+\>20 mmol/L
87
A 35 year old male body builder presents to **his GP surgery** with **genital atrophy.** **Routine blood** tests reveal that the patient is **hypokalamic.**
* **Use of Corticosteroids**
* Some of the **illegal artificial anabolic steroids** have some **mineralocorticoid activity.**
* The **genital atrophy** suggests that **it is an anabolic steroid.** Remember that **aldosterone** and **testosterone** are very similar, and the artificial ones have bizzare mixtures of effects.
88
**A 19 year old** female patient presents **to A&E** with severe dehydration, and is rapidly **infused.** Blood samples obtained by a train**ee nurse reveals gross hyponatraemia. Glucose levels** was also raised markedly.
Drip arm sample
89
A 45 year old female with long-term poorly controlled asthma presents to her GP complaining of weight gain and excessive sweating. A recent routine abdominal CT scan revealed atrophy of the adrenal glands.
Iatrogenic Cushing’s Syndrome
90
The next patient on the endocrine ward round has just received the results of **a high dose dexamethasone suppression test. T**he consultant informs you that the cortisol **levels have been suppressed** and asks you the most likely cause of this patient’s **cushingoid symptoms.**
## Footnote
**_Cushing’s Disease_**
91
A **35 year old** female arrives in **A&E at 16:30** in a very distressed state. Examination reveals tachycardia and **postural hypotension.** She complains of ongoing weakness and confusion following a recent operation on her knee. Blood tests reveal _**hyperkalaemia, hyponatraemia**._ Further tests measure cortisol levels at 50 nmol/L.
**_Addisonian Crisis_**
**_Causes_**
* sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison's, Hypopituitarism)
* adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
* steroid withdrawal
**_Management_**
* hydrocortisone 100 mg im or iv
* 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
* continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
* oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
92
A 52 year old male complains of muscle cramps and headaches. Examination reveals hypertension. Blood tests are ordered and reveal **a marked hypokalaemia.** The renin-aldosterone ratio is noted at 0.02 and the House Officer orders an abdominal CT scan.
Aldosterone Secreting Adrenal Adenoma
93
A 65 year old female presents to her new GP 5 years after an operation on her abdomen. She cannot remember the details of the operation but does remember that she was suffering from severe **Cushing’s Disease** at the time. She now notes a progressive **“tanning” of the skin**
Nelson Syndrome
94
What the results would be of low and high dose dexamethasone supression test:
Cushing syndrome caused by adrenal tumor:
Cushing Syndrome Related to ectopic ACTH:
Cushing Syndrome caused by pituitary tumor:
If there is not a normal response on the low-dose test, abnormal secretion of cortisol is likely **(Cushing's Syndrome)**. This could be a result of a cortisol-producing adrenal tumour, a pituitary tumour that produces ACTH, or a tumour in the body that inappropriately produces ACTH. THe high-dose test can help distinguish a pituitary cause (Cushing's Disease) from the others:
* **Cushine Syndrome** caused by an adrenal tumour: - low dose: no change - high dose: **NO CHANGE**
* **Cushing's Syndrome** caused related to ectopic ACTH producing tumour: - low dose: no change - high dose: **NO CHANGE**
* **Cushing's Syndrome** caused by pituitary tumour (Cushing's Disease): - low dose: no change - high dose: **NORMAL SUPPRESSION**
95
A 57 year old Type 1 diabetic woman presents with **weight loss, weakness** and **depression**. Examination reveals **postural hypotension, hyperpigmentation** in the palmar creases and **widespread patchy vitiligo**. Full blood count is unremarkable but U&Es reveal Na+ 130 mmol/l, K+ 6.0 mmol/l, Urea 7.4 mmol/l and Ca 2+ 2.70 mmol/l.
**Addisons:**
96
A 32 year old woman presents with a one year history of weight loss, fatigue and hirsutism. Examination reveals thin skin, easy bruising, purple abdominal striae and a supraclavicular fat pad. Plasma cortisol and ACTH levels are both raised but suppress after high dose dexamethasone suppression test.
Cushing's disease
97
A 64 year old man, who is known to suffer from ulcerative colitis, presents with a long history of weight gain, fatigue and depression. Examination reveals a moon-shaped face, centripetal obesity, thin skin and easy bruising. Serum cortisol levels are elevated and fail to suppress after low dose dexamethasone suppression test.
Iatrogenic Cushing
98
* A 21 year old man presents with rapid palpitations associated with **chest tightness,** **severe headache, tremor and sweating.**
* History reveals that the man had just consumed a large amount of alcohol.
**_Phaeochromocytoma_**
* A 21 year old man presents with rapid palpitations associated with **c_hest tightness,_** **_severe headache, tremor and sweating_**.
* History reveals that the man had just consumed a **_large amount of alcoho_**
* * **Phaeochromocytoma**
* Neuroendocrine tumour of the chromaffin cells of the adrenal medulla. Hypertension and hyperglycaemia are often found.
10% of cases are bilateral.
10% occur in children.
11% are malignant (higher when tumour is located outside the adrenal).
10% will not be hypertensive.
Familial cases are usually linked to the Multiple endocrine neoplasia syndromes (considered under its own heading).
Most tumours are unilateral (often right sided) and smaller than 10cm.
Diagnosis
Urine analysis of vanillymandelic acid (VMA) is often used (false positives may occur e.g. in patients eating vanilla ice cream!)
Blood testing for plasma metanephrine levels.
CT and MRI scanning are both used to localise the lesion.
Treatment
Patients require medical therapy first. An irreversible alpha adrenoreceptor blocker should be given, although minority may prefer reversible blockade(1). Labetolol may be co-administered for cardiac chronotropic control. Isolated beta blockade should not be considered as it will lead to unopposed alpha activity.
99
A 27 year old woman presents with a three month history **of weight gain**, deepening voice and secondary amenorrhoea. **Examination reveals clitoromegaly, acne, greasy skin and hirsutism. Serum cortisol is grossly elevated and ACTH levels are undetectable.**
**Adrenal carcinoma**
100
_**The commonest enzyme** deficiency seen **in CAH**_
**_21-Hydroxylase Deficiency_**
101
Levels of this steroid are raised in the serum of CAH patients
17-Hydroxyprogesterone
102
Increased levels are seen in the urine of CAH patients
Pregnanetriol
103
The sodium and potassium pattern seen in CYP21 deficiency (low aldestrone)
**Hyponatreamia** with **Hyperkalaemia**
104
A doctor suspecting his patient is suffering from **CAH** has just received some results that proves otherwise
**Normal ACTH levels**
105
An overweight 35-year old shop-assistant visits her GP complaining of debilitating tiredness. Her periods have also become infrequent in this time. Despite it being a warm day, she wears a coat and jumper inside. On examination, she has a symmetrical **painless lump on her neck**. The patient has a history of well-controlled **SLE.**
Hashimoto’s thyroiditis
106
A 33-year old overweight man complains of headaches and visual disturbances which he blames for two car accidents he has been involved in the last month. He has a ruddy appearance, and the GP notes that his weight is mainly concentrated in a ‘pot belly’. The man’s blood pressure is 150/100, and following a 48hr low –dose dexamethasone test, the patient has a cortisol of 500nm/L, and after a 48hr high-dose dexamethasone test, the cortisol was 250nmol/L
Cushing’s disease
107
Painful goitre following viral illness
De Quervain’s thyroiditis
108
A 15 year old overweight schoolgirl presents to her GP complaining of oligomenorrhoea. She is very self conscious and concerned about acne and excessive facial hair. Tests reveal raised serum LH and androgen concentrations.
Ovarian ultrasound
109
A 45 year old sales assistant presents with extreme tiredness. On examination, the GP notes !!**_a painless lump!!!_** on the front of her neck that moves up with swallowing, and that her hands are cold and dry. The patient has a history of pernicious anaemia.
**Hashimoto Thyroditids**
110
A 36 year old woman visits her GP, worried about the chest pain brought on by her daily run in the park. On examination, the GP notes dark patches on the backs of her hands. She mentions that her younger sister has the same dark patches. Serum cholesterol is 9.4 mmol/l.
**Familial hypercholesterolaemia**
**Familial hypercholesterolaemia (FH)** is an **AD** condition that is thought to affect around **1 in 500 people.** It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the gene which encodes the **LDL-receptor protein.**
Clinical diagnosis is now based on the Simon Broome criteria:
in adults total cholesterol (TC) \> 7.5 mmol/l and LDL-C \> 4.9 mmol/l or children TC \> 6.7 mmol/l and LDL-C \> 4.0 mmol/l, plus:
for definite FH: tendon xanthoma in patients or 1st or 2nd degree relatives or DNA-based evidence of FH
for possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels
111
An 11 year old boy is taken to the GP by his parents after complaining that “his wee-wee is a funny colour”. The parents reveal that their son hasn’t been too well lately, “He’s been very tired, feeling sick and has had temperature the last few days. We thought he’s just picked up a virus because he had a sore throat about 10days ago, but now that his urine has gone this smoky colour and **his eyes are puffy**, we thought we’d bring him in…”
Acute diffuse proliferative glomerulonephritis:
**Acute proliferative glomerulonephritis (post-streptococcal glomerulonephritisis) i**s caused by an infection with streptococcus bacteria, usually three weeks after infection, usually of the pharynx or the skin, given the time required to raise antibodies and complement proteins.[9][10] The infection causes blood vessels in the kidneys to develop inflammation, this hampers the renal organs ability to filter urine.[citation needed] Acute proliferative glomerulonephritis most commonly occurs in children.[10]
112
A gentleman who presented with **haemoptysis and haematuria**. Histology shows the accumulation of macrophages in Bowmans capsule. Immunology reveals the patient is **HLA-DR2**, and possesses Anti-glomerualr basement membrane antibody.
Goodpasture syndrome
| (pulonary-renal syndrome)
113
A 50 year old male with a persistant runny nose and sinusitis that is worsening. Immunology reveals circulating auto-antibodies against neutrophil cytoplasmic antigents (C-ANCA). Histology also shows the accumulation of macrophages in Bowmans capsule.
**Wegener's granulomatosis**
114
A 63 year old Scandanavian male presents with **_painless haematuria, fatigue, weight loss and fever_.** On examination a mass is found unilaterally in the loin. Family History reveals his father **had _Von Hippel-Lindau disease_.**
**_Clear cell renal carcinoma_**
**_Renal cell cancer_**
Renal cell cancer is also known as **hypernephroma** and **accounts for 85%** of **primary renal neoplasms.** It arises from proximal renal tubular epithelium
**_Associations_\***
* more common in middle-aged men
* smoking
* **von Hippel-Lindau syndrome**
* tuberous sclerosis
**_Features_**
* classical triad: haematuria, loin pain, abdominal mass
* pyrexia of unknown origin
* left varicocele (due to occlusion of left testicular vein)
* endocrine effects: may secrete erythropoietin (polycythaemia), parathyroid hormone (hypercalcaemia), renin, ACTH
* 25% have metastases at presentation
115
* **AD condition predisposing to neoplasia.**
**_Features_**
* cerebellar haemangiomas
* retinal haemangiomas: vitreous haemorrhage
* renal cysts (premalignant)
* phaeochromocytoma
* extra-renal cysts: epididymal, pancreatic, hepatic
* endolymphatic sac tumour
It is due to an abnormality in the **VHL gene** located on short arm of **chromosome 3**
116
**A 70year** old man being investigated f**or haematuria** and **loin discomfort** develops **dyspnoea.** *What X-ray presentation would you expect from that patient?*
**Cannonball metastases:**
* Multiple, round well-defined lung secondaries are often referred to as **'cannonball metastases'.**
* They are most commonly seen with **renal cell cancer** but may also occur secondary to **choriocarcinoma** and **prostate cancer.**
117
● Nephritic syndrome + sensorineural deafness + eye disorders (lens dislocation,
cataracts)
● Presents at 5-20yrs with nephritic syndrome progressing to ESRF
4. HEREDITARY NEPHRITIS (ALPORT’S SYNDROME)
● Hereditary glomerular disease caused by mutation in type IV collagen alpha 5 chain
● X linked
118
A 35-year-old alcoholic presents to A&E with confusion and maleana. On examination, he has signs of chronic liver disease and is pale and clammy. BP is 90/50mmHg and he has a weak thready pulse of 130bpm. Investigations reveal FBC: Hb 6.3g/dl, MCV 108fl, WCC 3.8 x 109/l, Plt 23 x 109/l; U&Es: Na+ 123mmol/l, K+ 4.4mmol/l, urea 27mmol/l, Cr 123umol/l.
Haemorrhage
119
A 61-year-old woman with kown p**eripheral vascular** and i**schaemic heart disease** is **started on an ACEi by her GP.**
3 weeks later she is admitted to hospital with i**ncreasing confusion and pruritis**. Investigations reveal FBC: Hb 12.3g/dl, MCV 85.2fl, WCC 6.8 x 109/l, Plt 403 x 109/l; U&Es: Na+ 130mmol/l, K+ 7.4 mmol/l, **urea 37mmol/l, Cr 841umo**l/l; urinalysis – protein ++, ketones +, blood nil.
What is the diagnosis?
**_Acute Renal Failure_**
A rapid loss of renal function manifesting as increased serum creatinine and urea.
Complications include **metabolic acidosis, hyperkalaemia, fluid overload, HTN,
↓Ca²+ and uraemia**
**RE-RENAL**
● Most common cause of acute renal failure
● Caused by renal hypo-perfusion e.g. hypovolaemia, sepsis, burns, acute pancreatitis, and renal artery stenosis.
120
An 84-year-old woman is found collapsed in her flat by a neighbour. She had a fall 3 days prior to her rescue and had been unable to get up or raise the alarm. On admission to hospital investigations reveal FBC: Hb 15.3g/dl, MCV 91.2fl, WCC 23.1 x 09/l, Plt 403 x 109/l; U&Es: Na+ 145mmol/l, K+ 7.1mmol/l, urea 32.9mmol/l, Cr 649umol/l; **CK 23,089iu/l.**
Rhabdomyolysis
121
* A 65 yr old lady with ischaemic heart disease and peripheral vascular disease presents at a&e with increasing confusion, hiccups and pruritus.
* She was started on ACE inhibitors a week ago.
**Renal Artery Stenosis**
122
## Footnote
A 21 yr old man is admitted to hospital with multiple fractures after his motorcycle collided into a lorry on the motorway. There is myoglobin in his urine
## Footnote
Acute tubular necrosis
\> 30 mmol/L Those patients would loose Na as consequence
123
A 50 yr old lady with **A BMI of 24** who had intermittent pain in the loin, with nausea and vomiting now has a low urine output and urinalysis shows microscopic **haematuria**.
**Renal obstruction**
124
A 45 yr old man with known renal problems **has bilateral leg oedema**. There is blood in his urine, and urine stix testing also confirms the presence of protein. **Microscopy also reveals red cell casts.**
**Nephritic Syndrome is charcterised by:**
**_Acute glomerulonephritis_** = nephritic syndrome which is manifestation of the glmoerular inflammation
-hematuria, dysmorphic RBC and red bllod cell casts in the urine
**_May also have:_**
Oliguria, Urea and Creatinei, Hypertension, Proteinuruia
125
A 62-year old man presents with **_lethargy_** and **_tiredness._**
He tells you that he is ‘on painkillers for back pain after a fall at work 6 weeks ago’. On examination **_he is pale_.** Blood tests reveal urea **_39.2 mmol/L_** (normal 1.7-8.3) and creatinine **_1158 μmol/L (normal 62-106)._**
His records show that he had a creatinine of **_90 μmol/L 3 months ago._**
**_Acute interstitial nephritis_**
126
A 40-year old man presents acutely unwell with back pain that radiates to his groin, and nausea and vomiting. He tells you he has seen blood in his urine. On examination he is febrile.
Ureteric stones
127
A poorly controlled 48-year old diabetic lady presents with a swollen face and ankles. Blood tests show albumin \<30g/L (normal 40g/L), ↑ cholesterol and normal creatinine. 24 hour urine collection reveals protein \>3g.
Nephrotic syndrome
128
A 25 year old man tells you he had dark brown urine after a sore throat and has since had microscopic haematuria. Renal biopsy reveals proliferation of the mesangium.
IgA nephropathy
129
One of the complications of chronic kidney disease which has ECG features of **peaked T waves**, **loss of the P wave** and **broad QRS complex**
**Hyperkalemia**
130
The gold standard for measuring glomerular filtration rate (GFR)
Inulin
131
Calculate the creatinine clearance for the following renal patient, following a 24 hour urine collection: urine volume 2litres; urine creatinine concentration 3mmol/l and plasma creatinine concentration 208 micro mol/l.
A.
20 mls/min
132
Calculate the **GFR** for the following renal patient, following a 24 hour urine collection: urine volume 2.7litres; urine creatinine concentration 2mmol/l and plasma creatinine concentration 107 micro mol/l.
35 mls/min
Creatine clearance = (creatinine's urine concentration)\* (Vol) / (plasma creatinine concentration) (note: the units have to match).
so, in this case:
Creatinine urine conc: 3mmol/l
Vol: 2l in 24hours: 1.39ml/minute
Plasma creatinine conc: 208micromol/l = 0.208mmol/l
so:putting this into the formula:
creat clearance = [(3mmol/l)\*(1.39ml/min)] / 0.208mmol/l
creatinine clearance = 20ml/min
Hope that was clear.
133
A good indicator of renal function
Serial creatinine readings
134
Reflects the muscle mass of a person
Serum creatinine
135
A **58-year** old man presents with **lethargy** and **generalised weakness.** He has a 2 year history of upper abdominal pain especially after meals and suffered a **myocardial infarct 3 years ago.**
Recently he has noticed swelling in his right first toe. Examination reveals tenderness in the epigastrium. No masses are felt and there is no organomegaly. Endoscopy reveals an active duodenal ulcer
**Low dose aspirin**
136
An 8 year old boy, showing signs of slow development, presents with a painful right knee which on examination was hot and swollen. Scratch marks on his face were also observed. An aspiration of the synovial fluid from the joint revealed crystals which were negatively birefringent.
Lesch-Nyhan Syndrome
137
What precipates gout?
T- alcohol metabolism to lactate contributes to urate Aspirin decreases the kidneys ability to excrete uric acid.
Thiazides are secreted by the organic acid transporter in the proximal tubule.
.
138
What type of **peptic ulcer** requires a **biopsy?**
tip: remember that **duodenal ulcers** are almost never malignant, but gastric ulcers may be **benign/malignant,** and therefore need a biopsy.
139
Chvostek’s sign and trousseau’s sign are positive in.....
Hypocalcaemia
140
A 20yr old gentleman presents to his GP with a lump in his neck. He has noticed the lump getting bigger. Examination reveals the lump to be in the thyroid gland. FNA and cytology reveals the diagnosis.
Papillary Carcinoma
141
Q: is there a difference between secondary hyperparathyroidism and renal osteodystrophy?
A: Renal osteodystrophy causes osteomalacia resulting from a def of 1,25(OH)Vit D (defective 1-hydroxylation due to the renal failure). Renal osteodystrophy ALSO leads to an increase in phosphate which reduces ionised Ca in the blood therefore inducing hyperparathyroidism. This then increases bone resorption by releasing Ca from bone stores. This is secondary hyperparathyroidism. If this becomes autonomous then it is termed tertiary hyperparathyroidism, which is biochemically no different to primary other than it is as a result of renal failure.
142
A 53 year old man presents with a loss of libido and erectile dysfunction.
Androgen insufficiency
143
A 32 year old woman presents to her GP with abdominal pain and nausea. She has also been feeling increasingly tired in the afternoon. On leaving her GP, she feels very faint and collapses.
Corticotrophin insufficiency
144
A 53 year old overweight woman presents with hypertension **(140 / 90mm Hg), a** triglyceride level of **160mg / dL** and a waist circumference of **39 inches.** She complains of **constant thirst** and **nocturia.**
Metabolic syndrome
145
A 6 year old boy presents with episodic abdominal pain and recurrent acute pancreatitis. The plasma is found to have a milky appearance and chylomicrons are found in the plasma following a period of fasting.
Lipoprotein lipase deficiency
146
A 45 year old woman presents with a history of weight gain, constipation and bradycardia. Cholesterol measurement is 6.7 m mol / L and plasma triglycerides are measured at 9mmol/L.
Hypothyroidism
147
The molecule that is formed by the gut after a meal and is the main carrier of dietary triglycerides
Chylomicron
148
This is present on capillaries of adipose tissue and skeletal muscle and it removes triglyceride from lipoproteins.
Lipoprotein lipase
149
The smallest lipoprotein which carries cholesterol from extra-hepatic tissues to the liver for excretion.
High density lipoprotein (HDL)
150
This molecule is present in the fasting state in cases of lipoprotein lipase deficiency.
Chylomicron
151
The first intermediate formed after VLDL particles synthesised by the liver are degraded.
Intermediate density lipoprotein
152
What are the priorities in lipid management of patients?
For "real-life purposes", the NCEP/ATPIII guidelines specify lipid management like this:
**1st priority** is bringing down LDL by \>30% (statins + ezetimibe \> other); there is evidence for benefit down to LDLs of 70mg/dL, cave bushmen have LDLs of ~40mg/dL.
**2nd priority i**s lowering TG (fibrates, niacin \> statins), unless TG are high enough to be risking pancreatitis in which case they become first priority.
**3rd is raising HDL**. (not officially even a priority because evidence is weaker and the best drug at doing it, niacin, is often intolerable)
153
How do daily requirements of water for neonates compare with those of adults?
.
\> 6 times adult requirements
154
High fluid intake in neonates during the first week of life is associated with increasing frequency of this condition.
Nectrotising enterocolitis
155
A 3-day-old baby presents **with jaundice** and **has raised levels of unconjugated bilirubin.** During examination, he is found to be irritable and has increased muscle tone and lies with an arched back (opisthotonus)
Kernicterus
156
An X-Ray performed on a preterm baby showed fraying, splaying and cupping of long bones. A blood test showed raised levels of this component.
Alkaline phosphatase
157
Pseudo **vitamin D deficiency 1** is associated with this defect.
Defect in renal hydroxylation
158
**An X-Ray** performed on a preterm baby showed **fraying, splaying and cupping** of long bones. A blood test showed raised levels of this component.
**Alkaline phosphatase**
4: The x-ray features are consistent with vitamin D deficiency. In vitamin D deficiency the alkaline phosphatase is typically raised. Alk phos is raised in many metabolic bone disease including hyperparathyroidism, rickets/osteomalacia and paget's. Note that in osteoporosis and multiple myeloma the ALP is typically normal. As an aside, in a child with x-ray features of vit D deficiency (metaphyseal flaring and osteopaenia) but a LOW ALP - think of hypophosphatasia.
159
a recognised cause of d**elayed _puberty secondary to hypogonadotrophic hypogonadism._** It is usually inherited as an X-linked recessive trait.
syndrome is thought to be caused by failure of **_GnRH-secreting neurons to migrate to the hypothalamus._**
The clue given in many questions _i_**_s lack of smell (anosmia) in a boy with delayed puberty_**
**_Kallman's syndrome_**
**Features**
* 'delayed puberty'
* hypogonadism, cryptorchidism
* anosmia
* sex hormone levels are low
* LH, FSH levels are inappropriately low/normal
* patients are typically of normal or above average height
* **Cleft lip/palate** and **visual/hearing defects** are also seen in some patients
160
A 3-week-old male is seen by a paediatrician because of severe jaundice that appeared at birth and has been worsening ever since.
Give me four causes.
Two with Conjugated and two with Unconjugated Bilirubin
Crigler-Najjar syndrome
161
A young boy presents to his GP with jaundice. He is also found to have h**aemoglobinuria, splenomegaly and anaemia.** His mother reveals that he was **jaundiced at birth** and needed a blood transfusion.
**G-PD Deficiency,**although I don't understand why this is not something else.
162
A 18 month old male is brought to the paediatrician by his mother because of repeated, **self-mutilating biting of his fingers** and li**ps and delayed motor development.** The patient’s mother has also noticed **abundant, orange-coloured “sand” (uric acid crystals)** in the child’s nappies.
**Lesch-Nyhan syndrome**
* hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency
* x-linked recessive therefore only seen in boys
* features: gout, renal failure, neurological deficits, learning difficulties, self-mutilation
163
An abnormality tested for by the Guthrie blood spot test
CHaMPS
Cystic Fibrosis
Hypothyroidism
MCAD
Phenylketonuria
Sicle Cell Diseae
164
An abnormaility that is tested for using electrophoresis
Sickle cell
165
A fatty acid oxidation defect
Medium chain acyl CoA dehydrogenase deficiency (MCAD)
166
An abnormality that may result in androgenisation and pigmentation among other signs and symptoms
**C**ongenital **A**drenal **H**yperplasia
167
A 2-month Canadian neonate presents with failure to thrive, jaundice and sepsis. You are screening for metabolic disorders, what 1st line test would you recommend?
Amino acids (urine and plasma)
## Footnote
Plasma and urine amino acids would be in first line metabolic screen.
The Canadian hint is trying to point towards Type 1 tyrosinaemia which is more common in Quebec.
(plus, the overlap between jaundice and sepsis suggest either tyrosinaemia or galactosaemia,
and it doesn't fit with the latter in other ways)
168
A male infant presents with **failure to thrive, neurological signs (**including tremor) **and tachypnea.** From our metabolic disorders screen, which 1st line test is likely to be abnormal?
Plasma ammonia.
) Tachypnoea with neuro signs suggests respiratory alkalosis and encephalopathy,
characteristic of urea cycle defects -
ie. ammonia would be raised.
169
170
A neonate has seizures, conjugated hyperbilirubinaemia and the 3rd year med student’s clinical observation is that “he looks weird!” From our metabolic disorders screen, which 1st line test is likely to be abnormal?
Very long chain fatty acids
## Footnote
3) Of the inborn errors, the 2 that produce dysmorphic signs are peroxisomal and congenital disorders of glycosylation.
Of these, only the first is associated with jaundice
171
A post mortem diagnosis of an inborn error of metabolism is investigated in a case of **“sudden infant death”.** What deficiency is the most likely cause?
MCAD
172
A neonate with a history of feeding difficulties presents with **jaundice, cataracts and sepsis**. What deficiency is the most likely cause?
Galactase-1-phosphate uridyl transferase
173
A neonate with a history of feeding difficulties presents with jaundice, cataracts and sepsis. What deficiency is the most likely cause?
As above jaundice suggests **galactosaemia** or **tyrosinaemia -**
In this case, cataracts occur because of accumulation of galacitol,
and jaundice because of excess galactose-1-phosphate in liver
174
In diabetics, this substance is formed in increased quantities in cells that do not require insulin for glucose uptake. It is injurious to those cells:
Sorbitol
175
50 year old male has serum glucose values of 145 and 167 mg/dL on visits to his physician last month. His body mass index is 31. He has not had any major illnesses. The islets of Langerhans in his pancreas may demonstrate:
amylodosis
176
An 11 year old girl has had a month-long course of **weight loss** despite eating and drinking large amounts of food and fluid. A urinalysis shows pH 5.5, sp gr 1.022, 4+ glucose, no blood, no protein, and 4+ ketones. What most likely prededed the clinical appearance of her disease:
**Insulitis**
177
An 11 year old girl has had a month-long course of weight loss despite eating and drinking large amounts of food and fluid. A urinalysis shows pH 5.5, sp gr 1.022, 4+ glucose, no blood, no protein, and 4+ ketones. What most likely prededed the clinical appearance of her disease:
Insulitis
178
179
GH, PRL, FSH. Which three anterior pituitary hormones are missing?
LH, ACTH, TSH
180
A CPFT confirms a diagnosis of hypopituitarism in Mr. Smith. What is the immediate treatment he should be given?
Cortisol replacement
181
A 53 year old man presents to his GP with headaches and poor eyesight. He has also noticed that his shoes are now too small for him. His GP tells him he thinks he should have a test done to detect the levels of a specific hormone in his blood. What is this hormone?
182
A 32 year old female complains for severe thirst. On further questioning she also suffers from mild depression, abdominal pains and has a history of broken bones. Her calcium levels are raised.
Primary hyperparathyroidism
183
A 45 year old smoker has recently been diagnosed with lung cancer. He has raised levels of calcium but low levels of PTH
Malignant hypercalcaemia
184
A 37 year old man has a round face, short metacarpals and metatarsals. He complains of mild depression and has a carpopedal spasm. Plasma PTH is raised and alk phos is slightly raised too.
Pseudohypoparathyroidism
185
A 45 year old smoker has recently been diagnosed with lung cancer. He has raised levels of calcium but low levels of PTH
Calcium in Malignacy
186
Hypercalcemia is common in cancer (occurs in 10-20% of patients). • **There are three main mechanisms of hypercalcemia in malignancy:**
**- PTH-rP related hypercalcemia** (80% of cancer pt.’s with hypercalcemia have PTH-rP-related hypercalcemia).
**- Osteolytic metastases** (Remember the mnemonic **BLT with a Kosher Pickle, Mustard & Mayo: Breast, Lung, Lymphoma, Thyroid, Kidney, Prostate, Multiple Myeloma**). Most commonly caused by breast cancer and non-small cell lung carcinoma - Tumor production of calcitriol (Hodgkin’s disease and in 1/3 of patients with NHL) • Most common cancers associated with hypercalcemia are breast cancer, lung cancer, and multiple myeloma. • Hypercalcemia in malignancy occurs abruptly, is severe, and portends a very poor prognosis.
For more information, see attached file.
187
**Osteolytic metastases:** - what is the mnemonic??
Remember the mnemonic **BLT with a Kosher Pickle, Mustard & Mayo**: Breast, Lung, Lymphoma, Thyroid, Kidney, Prostate, Multiple Myeloma).
188
A 50 year old woman presents with pain and stiffness in her hands. On further questioning she reveals that she also has pain in her back, hips and knees, which is worse in the evenings.
Osteoarthritis
189
A 50 year old man was admitted to hospital in a confused state. He was dyspnoeic and had a cough productive of sputum. He was unable to give a coherent history but one of the casualty officers knew him to be a type 1 diabetic patient with a history of COPD. Arterial blood: pH 7.18, pCO2 7.4kPa, Bicarbonate: 20
Mixed respiratory and metabolic acidosis
190
A young woman was admitted to hospital 8 hours after she had taken an overdose of aspirin. Arterial blood: H+ - 30nmol/L, pH – 7.53, pCO2 – 2.0kPa
Acute respiratory alkalosis with co-existent metabolic acidosis
191
A young woman was admitted to hospital unconscious, following a head injury. A skull fracture was demonstrated on radiography and a CT scan revealed extensive cerebral contusions. The respiratory rate was increased, at 38/min. 3 days after admission, the patient’s condition was unchanged. Arterial blood: H+ - 36nmol/L, pH – 7.44, pCO2 – 3.6kPa, Bicarbonate – 19mmol/L
Compensated respiratory alkalosis
192
A 45 year old man was admitted to hospital with a history of persistent vomiting, He had a long history of dydpepsia but had never sought advice for this, preferring to treat himself with proprietary remedies. On examination, he was obviously dehydrated and his respiration was shallow. Arterial blood: H+ - 28nmol/L, pH – 7.56, pCO2 – 7.2kPa, Bicarbonate – 45mmol/L. Serum: Na+ - 146, K+ - 2.8, Urea – 34.2. A barium meal showed pyloric stenosis, thought to be due to scaring caused by peptic ulceration.
Metabolic alkalosis with compensatory hypoventilation
193
A young man sustained injury to the chest in a road traffic accident. Effective ventilation was compromised by a large flail segment. Arterial blood: pO2 – 8kPa, pCO2 – 8kPa, pH – 7.24, H+ - 58nmol/L, Bicarbonate – 25mmol/L
Respiratory acidosis
194
Increases of what is a cardiovascular risk factor?
CRP
195
What is the major antagonist of serine proteases at a site of injury?
Alpha-1-antitrypsin
196
Which can act as a source of amino acids?
Albumin
197
A 60 year old male presents to his GP with symptoms of tiredness, dizziness and loss of vision. He has lymphadenopathy and splenomegaly. Serum electrophoresis shows an IgM spike.
**Waldenstrom's macroglobulinaemia**
198
Useful in staging and monitoring treatment of extracapsular spread of prostatic carcinoma
Acid phosphatase
199
Reflects increased osteoblastic activity and may be raised in osteomalacia and rickets
Alkaline phosphatase
200
Indicates a feature of biliary outflow obstruction rather than hepatocellular damage
Alkaline phosphatase
The best answer for exam purposes is that obstruction puts up alkaline phosphatase,
201
71 year old man has a 3 month history of severe back pain. On further questioning he has also experienced urinary frequency, dysuria, nocturia and has lost 6kg in the past 7 months. What enzyme would you expect to find elevated in this patient?
Alkaline Phosphatase
202
Raised in active sarcoidosis
Angiotensin converting enzyme (ACE)
203
Which enzyme rapidly rises post myocardial infarction but then rapidly declines and is a useful marker of reinfarction?
Creatine Kinase (MB)
204
Which enzyme would you expect to see decline late in **chronic pancreatitis?**
Amylase
205
A 55 year old man presents to A & E with a crushing **central chest pain** which radiates down his left arm. 3 hours later his blood tests show a large increase in a cardiac enzyme. This increase is still present when he is **discharged 3 days later.** Which enzyme is most likely to be raised?
troponin
206
A 53 year old woman presents to her GP because she has become increasingly tired recently. She also complains of itching which keeps her awake at night. On examination both scratch marks and signs of jaundice are found. Abnormalities in her blood tests include anti-mitochondrial antibodies. Which enzyme is most likely to be raised?
Liver Alkaline Phosphatase
207
A 45 year old woman with known gallstones presents to A & E with abdominal pain which radiates to her back. The pain is relieved by sitting forward. The pain has been constant for several hours and she has also vomited twice. Which enzyme is most likely to be raised?
Amylase
208
A 34 year old woman previously diagnosed with Hashimoto’s thyroiditis presents to her GP complaining of anorexia, amenorrhea and increasing fatigue.
On examination she is found to have palmar erythema. Her blood tests show anti-smooth muscle and anti-nuclear antibodies. Which enzyme is most likely to be raised?
AST
209
A 3-month-old boy was admitted to hospital with failure to thrive, and a persistent cough. On examination his height and weight were below the third centile. Subsequent immunological investigations have shown **marked T- and B-cell lymphopaenia** and **hypogammaglobulinaemia,** suggestive of severe combined immunodeficiency (SCID).
This disorder is frequently caused by a deficiency in which enzyme?
Adenosine deaminase (IL2)
210
A worried mother brings her obese 12 year old son to the GP, saying that he avoids exercise and has been recently found to be skipping his PE lessons. When confronted about this, the boy claimed that ‘it hurts when he exercises’. The skeptical GP was about to say ‘no pain, no gain’, when he remembered a lecture in medical school about McArdle’s glycogen storage disease (type V), which causes stiffness following exercise. He referred the boy for a muscle biopsy, which confirmed a deficiency in an enzyme involved in glycogen metabolism. Name this enzyme.
Mycophosphorylase
211
A young man presents with a history of recurrent febrile illness associated with painful parasthesiae in his hands and feet. On examination, you notice small red papules clustered in his pelvic and thigh region. **Urine dipstick shows protein +++.**
The patient complains that no doctor has been able to find out what is wrong with him. However, having recently passed your path exam, you suspect he might have Fabry’s disease, an X-linked disorder of glycolipid metabolism due to deficiency of which of the above?
Galctosidase A
212
A 40 year old woman is brought in by her husband. He explains that she has started getting up **during the night and going for walks and then forgetting her way home**. She says she has t**errible diarrhoea** day and night and she wakes to go to the toilet. On examination she has a tremor and you **see red scaly patches on her skin.** Which vitamin is she most likely to be deficient in?
Niacin B3
Demnetia
Dermititis
Diarrohoea
- also bullous lesions in sun exposed areas.
213
An 85 year old smoker lady is brought to the GP by concerned relatives. She lives alone and has become increasingly withdrawn. On close questioning it appears that over the past few months she has been smoking more heavily and surviving on little more than tea and toast.
Vitamin C deficiency
214
A 39 year old house wife is referred to clinic with a 6 month history of fatigue and depression, as well as "burning feet". She also gives a one month history of tingling in her fingers and toes at night
Vitamin B12 deficiency=Pernicious anemia
buring feet=peripheral neuropathy
215
A 38-year-old women presents with dyspepsia and shortness of breath on exercise. Blood tests show a severe anaemia, which on investigation is found to be megaloblastic. Gastric biopsies taken at endoscopy show severe atrophic gastritis, predominantly in the corpus. Anti-parietal cell antibodies are detected in the serum
Vitamin B12 (cobalamin
216
A 52-year-old man suffers from longstanding chronic pancreatitis. This has lead to steatorrhoea. He presents with recurrent epistaxis, malaena and haematuria. On examination he also has numerous bruises on his arms and shins.
Vitamin K
217
An eighty-year-old woman who lives alone is visited by social services after a worried neighbour says she has not seen her for a few months. On questioning she admits that she has hardly left her flat for four months as she has become increasingly agoraphobic. She has been surviving on tinned soup and crackers. Her GP finds she has swollen, bleeding gums, and bruises over her shins. Her skin shows a hyperkeratotic popular rash and petechial haemorrhages.
Vitamin C
218
A 65yr old female with blonde hair and blue eyes with a long history of rheumatoid arthritis and Hashimoto’s thyroiditis presents to her GP with tiredness and fatigue. On investigation her blood test shows an MCV of 125fl and a Hb of 9.4 g/dL. When looking under the microscope abnormally large reticulocytes (megaloblasts) were noted.
Vitamin B12 deficiency due to lack of intrinsic factor because of pernicious anaemia
219
A 35 yr old woman presents w**ith pain in her neck** which r**adiates to her upper neck**, j**aw and throat**. The pain is worse on swallowing. She has a Hx of an upper respiratory tract infection two weeks ago. On Ix she has a free T4 of 30pmol/l, free T3 of 11pmol/l and a TSH level of 0.1mU/l. On technetium scanning of the thyroid there is low iodine uptake.
Subacute granulomatous thryroiditis
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A 30 yr old woman presents with a Hx of weight loss, **diarrhoea, tremor and a marked swelling** at the front **of her neck.** On Ix she is found to have a TSH level of 0.05mU/l a free T4 level of 30pmol/l and a free T3 of 12pmol/l. On technetium scanning the thyroid shows increased iodine uptake.
**Grave’s Disease**
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A 25 year old male patient, in hospital with viral meningitis is found to have a slightly raised TSH and slightly low free T4.
**Sick euthyroid**
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A 70 yr old lady is found to have a tumour of the thyroid gland. She is also found to have high levels of circulating calcitonin
**Medullary thyroid cancer**
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32 year old female presented with **weight loss** and **anxiety**. The thyroid gland was enlarged, firm, fleshy and pale, infiltrated by lymphocytes. **Askanazy cells were noted.**
* **Hashimoto's thyroiditis:** **Askanazy cells** are associated with **hypothyroidism,** as is **lymphocytic infiltration** in the **thyroid gland.** And right again about **hashitoxicosis** (initially resembling hyperthyroidism).
* **Hashimoto's thyroiditis** (autoimmune hypothyroidism): At presentation, 75% of patients are euthyroid, 20% are hypothyroid, and 5% are hyperthyroid - a disease known as hashitoxicosis.
* About 50% eventually become hypothyroid because of destruction of the thyroid gland. ps **Remember association with hashimoto's and lymphoma. Ashkenazy cells.** See attached file for more info.
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22 yr old male presents with stridor. On examination, a multi-nodular thyroid is noted.
Simple colloid goitre
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A 12 yr old male presents with 1/7 of fever. Thyroid swelling and tenderness on palpation was noted. Histologically, the gland was infiltrated by neutrophils and lymphocytes. This child had not been vaccinated against the MMR.
**Giant cell thyroiditis**
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Autosomal dominantly inherited porphyria with neurovisceral manifestations only, resulting from porphobilinogen deaminase deficiency.
Acute intermittent porphyria
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Neurotoxic product(s) of heme breakdown producing damage in certain porphyrias acute intermittent porphyrias
## Footnote
5-aminolevulinic acid
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Autosomal dominantly inherited (or spontaneous mutation) porphyria with cutaneous manifestations only, resulting from uroporphyrinogen decarboxylase deficiency
Porphyria cutanea tarda
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Enzyme that catalyses the rate-limiting step of heme breakdown
ALA synthase
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Product(s) of heme breakdown resulting in photosensitivity (i.e. cutaneous) damage in certain porphyrias
Activated porphyrins and oxygen free radicals
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Recommended therapy used in an attack of acute intermittent porphyria,
Haem arginate
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Anti-inflammatory drug that is contraindicated in patients with porphyria
Diclofenac
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Drug that can result in chronic porphyria
Alcohol
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A second drug that is contraindicated in patients with porphyria that is not an NSAID
Co-trimoxazole
235
A 50 year old Asian woman is referred to the Diabetes clinic after presenting to her GP with polyuria and polydipsia. When tested, she has a fasting whole blood glucose of 6.3 mmol/L and 6.4 mmol/L when tested again a week later.
Diabetes Mellitus Type 2
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A 47 year old gentleman with a BMI of 29 had just started a new job that required a full medical by occupation health. He was found to have a fasting plasma glucose of 6.3 mmol/L.
Impaired Fasting Glucose
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A recently diagnosed 48 year old opera singer was noted by her diabetic nurse to have unacceptably high blood sugar levels, despite strict calorie control and oral metformin. Which class of drug could be added to reduce insulin resistance further?
Pioglitazone (Thiazolidinedione)
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A diabetic patient presents unconscious. Arterial blood gases reveal the following; pH 7.9 and paCO2 8.4. What is the metabolic abnormality.
Metabolic alkalosis
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A 48 year old man presents with pigmented skin, hyperglycaemia and a cushingoid appearance. A high dose dexamethasone test revealed there was a significant suppression of cortisol by day 2 of the test. What is the most likely cause of this glucocorticoid excess.
Cushing's disease
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A 65 year old man reports feeling lethargic and is found to have ‘impaired glucose tolerance’ by his GP.
Fasting plasma glucose 6.9 mmol/l. 2hrs post OGGT plasma glucose 10.5 mmol/l
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An obese 40 year old woman is found on a routine blood test to have ‘impaired fasting glucose’
Fasting whole blood glucose 6.0 mmol/l. Osmolarity 352 mOsm/kg.
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A 24 year old with type I diabetes is admitted to A + E with shortness of breath and a respiratory rate of 35. He is also drowsy.
Plasma glucose 1.45 mmol/l; pH 7.58; pCO2 2.4 kPa.
This patient has most likely taken excess insulin (or missed a meal after insulin), and has become hypoglycaemic. This leasd to anxiety/hyperventilation leads to respiratory alkalosis (high pH/ low pCO2). For a discussion on Q2, low Phosphate in rx of DKA and on whole blood vs plasma glucose see attached file.
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How to diagnose type II diabetes mellitius if patient is symptomatic
**If the patient is symptomatic:**
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
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Learn this graph
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what's the difference between impaired plasma glucose and impared glucose tolerance
**Impaired fasting glucose and impaired glucose tolerance**
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
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