Chemical Pathology Flashcards
(141 cards)
1
Q
Primary hyperparathyroidism caused by hyperplasia is associated with which gene
A
MEN1 (multiple endocrine neoplasia type 1)
2
Q
Is primary hyperparathyroidism more common in men or women?
A
Women
3
Q
The commonest cause of hypercalcaemia is
A
Primary hyperparathyroidism
4
Q
Blood results in primary hyperparathyroidism
PTH
Calcium
Phosphate
A
PTH inappropriately normal or high
Calcium high
Phosphate low
5
Q
Congenital absence of parathyroids is known as
A
DiGeorge syndrome
6
Q
Causes of low calcium due to low PTH
A
Surgical including post thyroidectomy
Auto-immune hypoparathyroidism
DiGeorge syndrome (congenital absence of parathyroids)
Mg Deficiency
7
Q
Formula for osmolality
A
Osmolality= cations+anions+urea+glucose
So
Osmolality= Na+K+Cl+HCO3+urea+glucose
since anions=cations this can be reduced to
Osmolality 2(Na+K) + Urea+ Glucose
8
Q
Formula for anion gap
A
Na + K - Cl - Bicarb
9
Q
Normal anion gap=
A
Approximately 18mM
10
Q
…+… injected is known as speedball
A
Cocaine
Heroin
11
Q
Acute dangers of cocaine:
A
Cardiac dysrhythmias, MI, Acute heart failure
12
Q
Fatal dose of methadone in a healthy adult:
A
60ml
13
Q
Fatal dose of methadone in a child
A
5ml
14
Q
Benzodiazepine antidote
A
flumazenil
15
Q
Problems with interpreting post-mortem blood toxicology
A
PM redistribution of drugs
Degradation of drugs post mortem e.g. cocaine
Individual variation in response (tolerance)
Site dependence
16
Q
Why use hair for post mortem toxicology?
A
Blood/serum, drugs typically can be detected for no more than 12 hours
Urine, drugs typically detected for 2-3 days
Hair is the only specimen can give information about long term drug use
Drugs are incorporated into hair from the blood stream during the growth phase
Hair growth approx 1cm/month – “tape-recording of drug use”
17
Q
Problems with hair analysis for post mortem toxicology
A
Environmental Contamination Absorbed from sweat or sebum coating hair Passive inhalation Cosmetic treatment Shampoo washing Perming, dyeing, bleaching Hair colour
18
Q
Most common causes of death after heroin use
A
Respiratory depression
Aspiration pneumonitis
19
Q
Applications of hair analysis (toxicology)
A
Applications of hair analysis
• Child custody cases
• Investigating spiked drinks defences
• Drug naïve deaths
• Monitoring drug use prior to return of driving license – Germany, Italy
• Investigation of drug use in exhumed/putrefied bodies
• Employment, pre-employment screening - USA
20
Q
Causes of metabolic acidosis
A
- Increased H+ production e.g. diabetic ketoacidosis
- Decreased H+ excretion e.g. Renal tubular acidosis
- Bicarbonate loss e.g. intestinal fistula
21
Q
Types of renal tubular acidosis. Brief pathogenesis
A
Type 1 is distal: due to failure of alpha cells in collecting ducts to secrete H+ into urine. Due to autoimmune e.g. RA, drugs e.g. lithium, genetics and hypercacliuric conditions e.g. hyperPTH
Type 2 is proximal: caused by decrease in bicarbonate reabsorption. Caused by genetics, amyloidosis, multiple myeloma, HAART (HIV meds), basically anything that causes deposits in kidneys.
Type 3: combo of 1 and 2. Not used.
Type 4: Caused by hypoaldosteronism or resistance to aldosterone e.g. CAH, primary hypoaldosteronism, NSAIDs, ACEi, Aldosterone blockers, sarcoidosis.
22
Q
Causes of metabolic alkalosis
A
Ingestion of bicarb
Reduced H+ excretion e.g. pyloric stenosis
Hypokalaemia
23
Q
Management of hypovolaemia hyponatraemia due to diuretics
A
Stop diuretic
0.9% NaCl
24
Q
Causes of euvolaemic hyponatraemia
A
SIADH
Hypothyroidism
Adrenal insufficiency
25
Causes of hypovolaemic hyponatraemia
Diuretics
Diarrhoea
Vomiting
Salt losing nephropathy
26
Causes of hypervolaemic hyponatraemia
Cirrhosis
Cardiac failure
Nephrotic syndrome
27
Features of SIADH
No hypovolaemia
High urine osmolality (over 100)
Low plasma osmolality
28
Causes of SIADH
CNS pathology
Lung pathology
Drugs (SSRI, TCA, opiates, PPIs, carbamazepine)
Tumours (most likely small cell lung cancers)
29
Investigations in suspected diabetes insipidus
Serum glucose (exclude diabetes mellitus)
Serum potassium (exclude hypokalaemia)
Serum calcium (exclude hypercalcaemia)
Plasma & urine osmolality (high plasma osmolality, and low urine osmolality)
Water deprivation test
30
Key features of ECG in hyperkalaemia
Peaked/tented T waves
Absent p waves
Broad complexes
31
Management of hyperkalaemia
10 ml 10% calcium gluconate
50 ml 50% dextrose + 10 units of insulin
Nebulised salbutamol
Treat the underlying cause
32
Features of primary hyperaldosteronism
Hypertension (resistant to treatment)
Low potassium
High sodium
High aldosterone, low renin (negative feedback)
33
Causes of hyperkalaemia
Renal impairment
Drugs (e.g. spironolactone, ACEi, A2RBs)
Adrenal insufficiency (Addison's disease)
Rhabdomyloysis
Acidosis (hydrogen moves into cells, potassium leaves cells)
Type 4 renal tubular acidosis (rare)
34
Drive for potassium secretion in distal nephron
Na reabsorption through ENaC (epithelial sodium channels) leads to tubular lumen negative electrical potential, driving potassium secretion.
Happens in the principal cells of the collecting tubule.
35
How does aldosterone increase potassium secretion?
Aldosterone increases transcription of genes for:
Epithelial sodium channels in collecting tubule (lumen side)
Basolateral sodium/potassium pumps in collecting tubule
So Na absorption is increased
Na reabsorption through ENaC (epithelial sodium channels) leads to tubular lumen negative electrical potential, driving potassium secretion.
36
Stimuli for aldosterone secretion
Angiotensin II
| Potassium
37
Causes of hypokalaemia
GI loss: D+V
Renal loss: Loop and thiazide diuretics, Barrter syndrome, Gitelman syndrome, excess aldosterone, excess cortisol
Redistribution into cells
38
What is Barrter syndrome
A rare inherited defect in the thick ascending limb of the loop of Henle.Causes low potassium levels. Caused by mutations in genes for multiple proteins leading to a similar outcome
39
What is Gitelman syndrome
Defect in Na/Cl co-transporters in distal tubule. Leads to hypokalaemia
40
Clinical features of hypokalaemia
Muscle weakness
Cardiac arrhythmia
Polyuria and polydipsia (nephrogenic DI, hypokalaemia makes you resistant to ADH)
41
Management of hypokalaemia
Serum potassium 3.0-3.5 mmol/L:
Oral potassium chloride (two SandoK tablets tds for 48 hrs)
Recheck serum potassium
Serum potassium 20 mmol per hour are highly irritating to peripheral veins
Treat the underlying cause e.g. give spironolactone for Conn's
42
Glucagon is not effective in patients with...
Liver failure
| They have no glycogen stores
43
```
Treatment for hypoglycaemia (acute) if:
Alert and orientated
Drowsy/confused but swallow intact
Unconconcious/ concerns about swallow
Deteriorating / refractory /insulin induced /difficult IV access
```
Rapid acting oral carbohydrates e.g. Lucozade
Buccal glucose e.g. hypostop
IV access: 50ml 50% glucose (Do not do this in real life!)
Consider IM/SC 1mg glucagon
44
Which patients (with diabetes) most commonly experience no symptoms with hypoglycaemia
Patients on B-blockers
| Patients who have recurrent hypoglycaemia
45
First response to hypoglycaemia (substance released/suppressed). Followed by...
Suppression of insulin
THEN
Release of glucagon
Release of adrenaline
Release of cortisol
46
End product of glycogen breakdown in muscle
Glucose-6 phosphate
47
C-peptide is
The cleavage product of pro-insulin (along with insulin).
| Secreted in equimolar amounts to insulin
48
Half life of c-peptide
| Half-life of insulin
4-6 minutes
| 30 minutes
49
The 3 ketone bodies
Acetone (pear drop smell in pts with DKA and is volatile), beta hydro and acetoacetate
50
Inherited metabolic disorders leading to hypoketotic hyooglycaemia in neonates
FAOD : no ketones produced
GSD type 1 ( gluconeogentic disorder)
Medium chain acyl coA dehydrogenase def.
Carnitine disorders
51
Beckwith Weidemann syndrome is...
An overgrowth disorder usually present at birth. Characterised by certain features including:
neonatal hypoglycaemia (islet cell hyperplasia)
macgroglossia
Macrosomia
Midline abdominal wall defects
Hepatoblastoma
Ear creases or ear pits
52
Mechanism of action of sulphonylureas
Bind to Sur 1 subunit of potassium channel (on insulin secreting cell) and cause it to close. Membrane depolarisation leads to insulin release
53
MEN1 is associated with tumours of the...
Pituitary
Parathyroid
Pancreas
54
How does Non-islet cell tumour cause hypoglycaemia
Tumour secretes "big IGF-2" which binds to IGF-1 receptors and insulin receptors. Produces downstream effects of insulin
55
Quinine causes hypoglycaemia by...
Stimulating insulin secretion
56
`Rate limiting step in haem biosynthesis
Creation of 5-Aminolaevulinic Acid (ALA) from succinyl-CoA and glycine.
Enzyme: ALA synthase
57
5-Aminolaevulinic Acid (ALA) created from glycine and CoA by ALA synthase. Next step in the haem biosynthesis pathway is...
ALA enters the cytoplasm and porphobilinogen formed from ALA by PBG synthase.
58
Principal sites of haem biosynthesis
Erythroid cells
| Hepatocytes
59
Differences between porphyrins and porphyrinogens
Porphyrinogens are raised in porphyria
Colourless compounds
Unstable and readily oxidised to the corresponding porphyrin by the time urine /faeces reaches lab
Porphyrins are highly coloured (detected in urine or faeces)
Porphyrins near start of the pathway are water soluble – urine (uro-)
Porphyrins near end less soluble – faeces (copro-)
60
Deficiency in ALA synthase causes...
Sideroblastic aneamia (inability to incorporate iron into haemoglobin, form sideroblasts)
Presents acutely with neurovisceral attacks:
skin paleness, fatigue, dizziness, and enlarged spleen and liver. Heart disease, liver damage, and kidney failure can result from iron buildup in these organs
NOT A PORPHYRIA
61
PBG synthase deficiency causes...
Acute porphyria. Specifically ALA dehydratase/plumboporphyria
Extremely rare form of porphyria
Build-up of ALA, but not PBG
Diagnostic implications – with a porphyria the Uroporphyrinogen in the urine is measured. However with this deficiency, there is no Uroporphyrinogen produced and therefore cannot be detected.
62
HMB synthase deficiency causes
Acute intermittent porphyria.
```
Neurovisceral attacks:
Abdo pain and vomiting
Tachycardia and hypertension
Constipation, urinary incontinence
Hyponatraemia +/- seizures (thought to be due to SIADH)
Psychological symptoms
Sensory loss / muscle weakness
Arrythmias / cardiac arrest
```
No skin symptoms: No production of porphyrinogens
63
Mode of inheritence of acute intermittent porphyria
Autosomal dominant
64
Neurotoxic haem precursor
5-Aminolaevulinic Acid (ALA)
65
Precipitating factors for acute intermittent porphyria
```
ALA synthase inducers
Barbiturates, steroids, ethanol, anticonvulsants
Stress
Infection, surgery
Reduced caloric intake
Endocrine factors
More common in women and premenstrual
Just started OCP (classic examination)
```
66
Treatment of acute intermittent porphyria
Avoid attacks
Adequate nutritional intake (high carb diet)
Precipitant drugs
Prompt treatment infection/illness
iv carbohydrate
iv haem arginate
Suppresses pathway from the top
67
Signs/symptoms of acute intermittent porphyria
```
Neurovisceral attacks
Abdo pain and vomiting
Tachycardia and hypertension
Constipation, urinary incontinence
Hyponatraemia +/- seizures (thought to be due to SIADH)
Psychological symptoms
Sensory loss / muscle weakness
Arrythmias / cardiac arrest
```
68
Acute porphyrias that cause skin lesions
Hereditary coproporphyria
| Variegate porphyria
69
Signs and symptoms of hereditary coproporphyria
```
Neurovisceral attacks:
Constipation and urinary incontinence
Abdo pain and vomiting
Tachycardia and hypertension
Arrhythmia/ cardiac arrest
Seizures
Psychological symptoms
Sensory loss/ muscle weakness
```
Skin:
Blistering
Skin fragility
70
Mode of inheritence of coproporphyria
Autosomal dominant
71
Consequence of coproporphyrinogen deficiency
Acute porphyria: specifically hereditary coproporphyria
| Neurovisceral attacks and skin symptoms
72
Consequence of protoporphyrinogen deficiency
Acute porphyria: Specifically variegate porphyria
73
Main type of acute porphyria
Acute intermittent porphyria
74
Mode of inheritance of variegate porphyria
Autosomal dominant
75
Signs symptoms of variegate porphyria
```
Neurovisceral attacks
Abdo pain and vomiting
Constipation and urinary incontinence
Seizures
Sensory loss and muscle weakness
Psychological symptoms
Tachycardia and Hypertension
Arrhythmias/cardiac arrest
```
Skin symptoms
Photosensitivity
Skin fragility
Blistering
76
How do we use urine and stool testing to differentiate the acute porphyrias
In plumboporphyria tere will be no porphobilinogen produced and no uroporphyrinogen produced (so no porphyrins in stool or urine)
In AIP, VP, and HCP PBG is raised but:
Porphyrins raised in HCP or VP, but not AIP
77
Consequence of uroporphyrinogen III synthase deficiency
| .
Congenital erythropoietic porphyria. A non-acute porphyria
78
Consequence of uroporphyrinogen decarboxylase deficiency
Porphyria cutanea tarda. A non-acute porphyria
79
Consequence of ferrochetolase deficiency
Erthropoietic porphyria. A non-acute porphyria.
80
Signs and symptoms of porphyria cutanea tarda
Formation of vesicles on sun-exposed areas of skin crusting, superficial scarring, pigmentation
81
Biochemical features of porphyria cutanea tarda
Urinary and plasma uroporphyrins increased.
| Ferritin increased
82
Precipitants of porphyria cutanea tarda
Alcohol
Oestrogen
Hepatic compromise (e.g. hepatitis infection)
83
Features of erythropoetic porphyria
Photosensitivity only, no blisters
Only erythroid cells affected, therefore need to measure RBC protoporphyrin
Caused by ferrochetolase deficiency. Raised RBC protoporphyrin is the result.
84
Features of congenital erythropoietic porphyria
Deficiency of uroporphyrinogen III synthase
Raised HMB
Skin features:
Formation of vesicles that can rupture
Photosensitivity
Haemolytic anaemia
Porphyrins additionally accumulate in the bone and teeth, resulting in erythrodontia (red discolouration of teeth)
Very acute attacks:
Vomiting and constipation can follow attacks
85
Reactions catalysed by ALT and AST
The transfer of the alpha-amino groups of alanine and aspartate, respectively, to the alpha-keto group of ketoglutarate, which results in the formation of pyruvate and oxaloacetate.
86
Reaction catalysed by gamma GT
Gamma-glutamyl transpeptidase (GGT) catalyzes the transfer of the gamma-glutamyl group from gamma-glutamyl peptides such as glutathione to other peptides and to L-amino acids
87
Gamma GT is elevated in...
Chronic alcohol use
Bile duct disease
Hepatic metastases
88
ALP markedly rises in...
```
Obstructive jaundice or bile duct damage
Bone disease (especially metastatic and pregnancy)
```
89
Causes of low albumin
low production (chronic liver disease, malnutrition)
loss (eg gut, kidney)
sepsis (“3rd spacing”)
90
Alpha-feto protein raised in...
HCC
Hepatic damage/regeneration
Pregnancy
Testicular cancer
91
Bilirubin is conjugated with
Glucuronic acid
92
In pre-hepatic jaundice bilirubin is (conjugated/unconjugated)
Unconjugated
93
In hepatic jaundice bilirubin is (conjugated/unconjugated)
Both
94
In post hepatic jaundice bilirubin is...
Conjugated
95
Post-hepatic causes of jaundice
Bile duct obstruction
| Drugs
96
Hepatic causes of jaundice
Genetic (e.g. Gilbert's)
Hepatitis
Drug reaction
97
Pre-hepatic causes of jaundice
Haemolysis
98
Bilirubin in urine is (conjugated/unconjugated)
Conjugated (but should not be present)
99
Urobilinogen in urine is raised in...
haemolysis, hepatitis, sepsis
100
What is Courvoisier’s Sign
In the presence of a painless palpable gallbladder, jaundice is unlikely to be caused by gall stones
101
Mode of inheritance of Gilbert's syndrome
Autosomal recessive
102
Effect of vitamin A
a) excess
b) deficiency
a) Colour blindness
| b) Exfoliation and hepatitis
103
Effect of vitamin A
a) deficiency
b) excess
Rickets/osteomalacia
| Hypercalcaemia
104
Effect of vitamin E (tocopherol)
a) Deficiency
b) Excess
a) Anaemia and neuropathy. Possibly malignancy/IHD
| b) None
105
Effect of vitamin K (phytomenadione)
a) deficiency
b) Excess
Defective clotting
| None
106
Effect of vitamin B1 (thiamine)
a) Deficiency
b) Excess
Beri-beri, Neuropathy and Wernicke syndrome
| None
107
Effect of vitamin B2 (riboflavin)
a) Deficiency
b) Excess
Glossitis
| None
108
Effect of vitamin B6 (pyridoxine)
a) Deficiency
b) Excess
Dermatitis and anaemia
| Neuropathy
109
Effect of vitamin B12
a) Deficiency
b) Excess
```
Perninicious anaemia (macrocytic anaemia)
None
```
110
List tests for vitamin B enzymes
B1 (thiamine): RBC transketolase
B2 (riboflavin): RBC glutathione reductase
B6 (pyridoxine): RBC AST activation
B12 (cobalamin): serum B12
111
Effect of vitamin C (ascorbate)
a) Deficiency
b) Excess
Scurvy
| Renal stones
112
Effect of folate
a) Deficiency
b) Excess
a)Megaloblastic anaemia
Neural tube defects in foetus
b) None
113
Effect of niacin
a) Deficiency
b) Excess
a) Pellagra
| b) None
114
Excess fluoride causes...
Fluorosis: characterised by mottling of the teeth and if severe calcification of the ligaments
115
Effect of copper
a) Deficiency
b) Excess
Anaemia
| Wilson's
116
Effect of zinc
a) Deficiency
b) Excess
Dermatitis
| None
117
Ideal diet contains 50%....
carbohydrate
118
Definition of overweight and obese according to BMI
25-30 kg/m2 overweight
>30 kg/m2 obese
>40 kg/m2 morbidly obese
119
Metabolic syndrome is...
Metabolic syndrome is a clustering of at least three of five of the following medical conditions:
abdominal (central) obesity,
elevated blood pressure,
elevated fasting plasma glucose,
high serum triglycerides,
low high-density lipoprotein (HDL) levels.
120
Marasmus is...
Marasmus is a form of severe malnutrition characterized by energy deficiency.
It occurs before the age of 1
Marasmus is commonly represented by a shrunken (growth retardation), wasted appearance, loss of muscle mass and subcutaneous fat mass.
121
Kwashiorkor is
A form of severe protein–energy malnutrition characterized by oedema, irritability, ulcerating dermatoses, and an enlarged liver with fatty infiltrates.
Sufficient calorie intake, but with insufficient protein consumption, distinguishes it from marasmus.
Kwashiorkor cases occur in areas of famine or poor food supply
122
Key features of kwashiorkor
```
Oedematous
Scaling/ulcerated
Lethargic
Large liver, s/c fat
Protein deficient
```
123
Emergency treatment of hypercalcaemia
```
Ca2+ >3.0 mmol/L &/or unwell
(Dehydrated, confused, drowsy, coma, seizures, renal failure)
IV access (venflon/central line)
Catheter
Rehydrate: 0.9% saline (can be litres++)
Initiate calciuresis:
0.9% saline
Frusemide
IV pamidronate 30 - 60 mg if cause is cancer (hold off)
```
124
Non emergency treatment of hypercalcaemia
Keep well hydrated
Avoid thiazides
Surgery
125
What are brown tumours?
The brown tumor is a bone lesion that arises in settings of excess osteoclast activity, such as hyperparathyroidism. It is not a true neoplasm
Brown tumours consist of fibrous tissue, woven bone and supporting vasculature, but no matrix.
The osteoclasts consume the trabecular bone that osteoblasts lay down and this front of reparative bone deposition followed by additional resorption can expand beyond the usual shape of the bone, involving the periosteum thus causing bone pain.
The characteristic brown coloration results from hemosiderin deposition into the osteolytic cysts.
Hemosiderin deposition is not a distinctive feature of brown tumors; it may also be seen in giant cell tumors of the bone
126
Brown tumours are seen in which condition
Hyperparathyroidism
127
In sarcoidosis PTH is...
suppressed to undetectable levels
128
Treatment of sarcoidosis
Steroids
129
Cause of hypercalcaemia in sarcoidosis...
Systemic disease where macrophages express 1 alpha hydroxylase (which activates vitamin D)
So calcium is higher in summer
130
Cause of seasonal hypercalcaemia...
Sarcoidosis
131
Gold-standard measure of GFR
Inulin clearance
132
Urine microscopy:
| Urine is examined to look for:
```
Crystals
Red blood cells
White blood cells
Casts
Bacteria
```
133
About 80% of kidney stones are partially or entirely formed of...
Calcium oxalate
134
Causes of pre-renal AKI
```
True volume depletion
Hypotension
Oedematous states
Selective renal ischaemia
Drugs affecting glomerular blood flow
```
135
Causes of post renal AKI
```
Ureteric obstruction (bilateral)
Prostatic / Urethral obstruction
Blocked urinary catheter
```
136
Commonest causes of CKD
```
Diabetes
Atherosclerotic renal disease
Hypertension
Chronic Glomerulonephritis
Infective or obstructive uropathy
Polycystic kidney disease
```
137
Consequences of CKD
```
1]Progressive failure of homeostatic function
-Acidosis
-Hyperkalaemia
2]Progressive failure of hormonal function
-Anaemia
-Renal Bone Disease
3]Cardiovascular disease
-Vascular calcification
-Uraemic cardiomyopathy
4]Uraemia and Death
```
138
Consequences of renal acidosis
- Muscle and protein degradation
- Osteopenia due to mobilization of bone calcium
- Cardiac dysfunction
139
Features of hyperkalaemia ECG
Tall peaked t wave
Prolonged pr interval
Widened flattened p waves (eventually disappear)
Widened QRS (with tall T wave)
140
Treatment of CKD bone disease
```
Phosphate control
-Dietary
-Phosphate binders
Vit D receptor activators
-1alpha calcidol
-Paricalcitol
Direct PTH suppression
-Cinacalcet
```
141
3 phases of uraemic cardiomyopathy
LV hypertrophy
LV dilatation
LV dysfunction
