Chemical Pathology- Part 2 (p85-100- Adrenals, calcium, enzymes, nutrition, metabolic disorders, sugar, paeds + renal) Flashcards
(155 cards)
1
Q
What are the common causes of Cushing’s syndrome?
A
Pituitary tumour- Cushing’s disease 85%
Adrenal tumour 10%
Ectopic ACTH producing tumour 5%
Iatrogenic steroid use
2
Q
Common symptoms and signs of Cushing’s?
A
Moon face Buffalo hump Striae Acne HTN Diabetes Muscle weakness- proximal myopathy Hirsutism
3
Q
What are the investigations to diagnose Cushing’s?
A
Low dose dexamethasone- 0.5mg- will fail to suppress cortisol in all causes of Cushing’s
High dose dexamethasone 2mg- will suppress pituitary cushing’s
4
Q
How do you treat Cushing’s?
A
Treat underlying disease- e.g. surgical removal of lesion
5
Q
What causes Addison’s?
A
Autoimmune TB Tumour mets Adrenal Haemorrhage Amyloidosis
6
Q
What are the symptoms and signs of Addison’s?
A
Increased K+ Decreased Na+ + Glucose Postural hypotension Skin pigmentation Lethargy Depression
7
Q
What investigations are used to diagnose Addison’s?
A
SynACTHen test
8
Q
How do you treat Addison’s?
A
Hormone replacement- hydrocortisone/fludrocortison if primary lesion
9
Q
What causes Conn’s?
A
Adrenal tumour
10
Q
What are the symptoms and signs of Conn’s?
A
Uncontrollable HTN
Raised Na+
Decreased K+
11
Q
What investigations are used to diagnose Conn’s?
A
Aldosterone:Renin ratio high
12
Q
How do you treat Conn’s?
A
Aldosterone antagonists/potassium sparing diuretics- spironolactone, eplerenone, amiloride
13
Q
What causes phaeo?
A
Adrenal medulla tumour leading to increased adrenaline
14
Q
What are the symptoms and signs of phaeo?
A
Hypertension
Arrhythmias
Death if untreated
15
Q
What investigations are used to diagnose phaeo?
A
Plasma and 24h urinary metadrenaline measurement/catecholamines + VMA (vanillylmandelic acid)
16
Q
How do you treat phaeo?
A
Alpha blockade
Beta blockade
Surgery when blood pressure is well controlled
17
Q
What is phenytoin used to treat?
A
Seizures
18
Q
What is digoxin used to treat?
A
Arrhythmias
19
Q
What is lithium used to treat?
A
Relapse of mania in BPAD
20
Q
What are the signs of phenytoin toxicity?
A
Ataxia and nystagmus
Treated with omission or reduction of dose
21
Q
What are the signs of digoxin toxicity and how is it treated?
A
Arrhythmias
Heart block
Confusion
Xanthopia (seeing yellow)
Treated with digibind aka digoxin immune Fab
22
Q
What are the signs of lithium toxicity?
A
Tremor (early) Lethargy Fits Arrhythmia Renal failure- treated with haemodialysis
23
Q
What are the signs of gentamicin toxicity?
A
Tinnitus
Deafness
Nystagmus
Renal failure
Treated with omission or reduction of dose
24
Q
What are the signs of theophyline toxicity?
A
Arrhythmia
Anxiety
Tremor
Convulsions
Treated with omission or reduction of dose
25
Normal plasma range of calcium?
2.2-2.6mmol/l
26
How does calcium exist in the blood in terms of bound/free etc?
45% ionised (free- biologically active)
| 50% bound to albumin, therefore affected by albumin level- use corrected calcium
27
What does Parathyroid Hormone (PTH) do?
Increased tubular 1a hydroxylation of vit D (25(OH)D) to form calcitriol
Mobilises calcium and PO4 from bone
Increased renal calcium reabsorption
Increased renal phosphate excretion
28
What does calcitriol (1,25 (OH)2D) do?
Increased calcium and phosphate absorption from the gut
29
What causes PTH release?
Decreased plasma Ca
30
What is the primary defect in 1' hyperparathyroidism?
Increase of PTH (80% parathyroid adenoma)
31
What is the primary defect in 2' hyperparathyroidism?
Renal osteodystrophy
32
What is the primary defect in 3' hyperparathyroidism?
Autonomous PTH secretion post renal transplant
33
What is the primary defect in hypoparathyroidism?
Low levels of PTH
1'- DiGeorge syndrome
2'- Post-thyroid surgery
34
What is the primary defect in Rickets/osteomalacia?
Vit D deficiency
35
What is the primary defect in osteoporosis?
Bone loss
36
What would you see in 1' hyperparathyroidism in terms of Ca, PO4, PTH, ALP + Vit D?
```
Increased Ca
Decreased PO4
Increased/Normal PTH
Increased/Normal ALP
Normal Vit D
```
37
What would you see in 2' hyperparathyroidism in terms of Ca, PO4, PTH, ALP + Vit D?
```
Decreased/Normal Ca
Increased PO4
Increased PTH
Increased ALP
Normal Vit D
```
38
What would you see in 3' hyperparathyroidism in terms of Ca, PO4, PTH, ALP + Vit D?
```
Increased Ca
Decreased PO4
Increased PTH
Increased/Normal ALP
Normal Vit D
```
39
What would you see in hypoparathyroidism in terms of Ca, PO4, PTH, ALP + Vit D?
```
Decreased Ca
Increased PO4
Decreased PTH
Decreased/Normal ALP
Normal Vit D
```
40
What would you see in Rickets/Osteomalacia in terms of Ca, PO4, PTH, ALP + Vit D?
```
Decreased Ca
Decreased PO4
Increased PTH
Increased ALP
Decreased Vit D
```
41
What would you see in Paget's in terms of Ca, PO4, PTH, ALP + Vit D?
```
Normal Ca
Normal PO4
Normal PTH
Increased ALP
Normal Vit D
```
42
What would you see in osteoporosis in terms of Ca, PO4, PTH, ALP + Vit D?
```
Normal Ca
Normal PO4
Normal PTH
Normal ALP
Normal Vit D
```
43
What are the causes of hypocalcaemia with increased phosphate?
CKD
Hypoparathyroidism (inc post-thyroid surgery)
Pseudohypoparathyroidism
Hypomagnesaemia
44
What are the causes of hypocalcaemia with normal or decreased phosphate?
Osteomalacia
Acute pancreatitis
Overhydration
Respiratory alkalosis
45
Symptoms of hypocalcaemia?
Perioral paraesthesia
Carpopedal spasm
Neuromuscular excitability- Chvostek's + Trousseau's
46
What is Chvostek's sign?
Abnormal reaction due to stimulation of facial nerve due to existing nerve hyperexcitability in hypocalcaemia
47
What is Trousseau's sign?
Carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes in hypocalcaemia
48
What is the treatment of mild and severe hypocalcaemia?
Mild- give calcium
| Severe- 10% calcium gluconate IV
49
Causes of hypercalcaemia?
Dehydration
Primary or tertiary hyperparathyroidism
With raised ALP and phosphate- Bone mets, thyrotoxicosis + sarcoidosis
With normal ALP and raised phosphate- myeloma, excess vit D, sarcoid, milk alkali syndrome
50
Symptoms of hypercalcaemia?
```
Stones (renal)
Bones (Pain)
Groans (psych)
Moans (abdo pain)
Polyuria
Muscle weakness
```
51
How do you treat hypercalcaemia?
Correct dehydration
Bisphosphonates
Correct cause e.g. chemo for cancer
52
What are the RFs for renal stones?
Dehydration
Abnormal urine PH (meat intake, renal tubular acidosis)
Increased excretion of stone constituents
Urine infection
Anatomical abnormalities
53
What are the common constituents of renal stones?
```
Calcium- mixed 45%
Calcium oxalate 35%
Calcium phosphate 1%
Triple phosphate "Struvite" 10%
Uric acid 5%
Cysteine 1-2%
```
54
Which types of renal stones are radiolucent?
Uric acid
| Cysteine
55
Which renal stones have a 'staghorn' appearance
Triple phosphate "Struvite"
56
What marker would be 10x upper limit of normal serum levels in acute pancreatitis?
Amylase
57
What is Creatine Kinase a marker of?
Muscle damage
58
Which creatine kinase is a marker of skeletal muscle damage and which is a marker of cardiac muscle damage?
CK-MM = skeletal muscle
| CK-MB (1+2)= cardiac muscle
59
What causes raised CK levels physiologically?
Race- Afro-Caribbean
60
What causes raised CK levels pathologically?
DMD (>10x ULN)
MI (>10x ULN)
Statin myopathy
Rhabdomyolysis
61
Where is alkaline phosphatase high in concentrations?
Liver
Bone
Intestine
Placenta
62
What are the physiological causes of raised ALP?
Pregnancy (3rd trimester)
| Childhood during growth spurt
63
What are the pathological causes of raised ALP (Bone + Liver)?
```
>5x ULN-
Bone- Pagets, Osteomalacia
Liver- Cholestasis, Cirrhosis
<5x ULN-
Bone- tumours, fractures, osteomyelitis
Liver- infiltrative disease + hepatitis
```
64
What is the biomarker of myocardial injury?
Troponin I/T
65
When do you test Troponin?
6h and 12h post onset of chest pain
66
How long does Troponin remain elevated for?
3-10d
67
What is one international unit?
The quantity of enzyme that catalyses 1uMol of substrate in a minute- measure of MASS or CONCENTRATION
68
What does PCSK9 do?
Binds LDLR and promotes its degradation leading to raised LDL
Loss of function mutation leads to low LDL- novel LDL-therapy is Anti-PCSK9 MAb
69
Which vitamins are fat soluble?
ADEK
70
Which vitamins are water soluble?
B1 (thiamine), B2 (riboflavin), B6 (pyroxidine), B12 (cobalamin), C, Folate, B3 (Niacin)
71
What does Vit A deficiency lead to?
Colour blindness
72
What does Vit D deficiency lead to?
Osteomalacia/Rickets
73
What does Vit E deficiency lead to?
Anaemia/neuropathy
| ?Malignancy/IHD
74
What does vit K deficiency lead to?
Defective clotting
75
What does excess vit A lead to?
Exfoliation
| Hepatitis
76
What does excess vit D lead to?
Hypercalcaemia
77
What does vit B1 (thiamine) deficiency lead to?
Beri-Beri
Neuropathy
Wernicke syndrome
78
How do you test vit K?
PTT
79
What does B2 (riboflavin) deficiency lead to?
Glossitis
80
What does B6 (pyroxidine) deficiency lead to?
Dermatitis/anaemia
81
What does B6 excess lead to?
Neuropathy
82
How do you test B2 (riboflavin)?
RBC glutathione reductase
83
How do you test B6 (pyroxidine)?
RBC AST activation
84
What does B12 deficiency lead to?
Pernicious anaemia
85
How do you test B12?
Serum
86
What does vit C deficiency lead to?
Scurvy
87
What does excess vit C lead to?
Renal stones
88
What does folate deficiency lead to?
Megaloblastic anaemia
| Neural tube defect
89
What does B3 (niacin) deficiency lead to?
Pellagra- 3Ds (Dementia, dermatitis, diarrhoea)
90
What does iron deficiency lead to?
Hypochromic anaemia
91
What does iron excess lead to?
Haemochromatosis
92
What does iodine deficiency lead to?
Goitre
| Hypothyroid
93
What does zinc deficiency lead to?
Dermatitis
94
What does copper deficiency lead to?
Anaemia
95
How do you test copper?
Cu
| Caeroplasmin
96
What is the Guthrie blood spot test and what does it test for?
Heel prick in neonates to screen for serious conditions, mainly metabolic e.g. CF, phenylketonuria, congenital hypothyroidism, medium chain acylcoA dehydrogenase deficiency
97
What causes phenylketonuria?
Phenylalanine hydroxylase deficiency
98
How do you screen for phenylketonuria?
Phenylalanine levels
99
What happens in cystic fibrosis?
Mutation in CFTR- viscous secretions -> ductal blockages
100
How do you screen for cystic fibrosis?
Immune reactive trypsin
| If positive -> DNA mutation detection
101
What happens in medium chain acylcoA dehydrogenase deficiency?
Fatty acid oxidation disorder
102
How do you screen for medium chain acylcoA dehydrogenase deficiency?
Acylcarnitine levels by tandem mass spectrometry
103
What is the definition of specificity?
The probability in % that someone without the disease will correctly test negative
TN/FP+TN
104
What is the definition of sensitivity?
Probability that someone with the disease tests correctly positive
TP/TP+FN
105
What is the definition of PPV?
Probability that someone who tests positive actually has the disease
TP/TP+FP
106
What is the definition of NPV?
Probability that someone who tests negative actually doesn't have the disease
TN/TN+FN
107
What are the 5 different groups of metabolic conditions?
```
1- Accumulation of toxins
2- Reduced energy stores
3- Large molecule synthesis
4- Defects in large molecule metabolism
5- Mitochondrial
```
108
Give examples of metabolic conditions with accumulation of toxins?
Organic acidaemias
Urea cycle disorders
Aminoacidopathies (e.g. PKU + maple syrup urine disease)
109
Give examples of metabolic conditions with reduced energy stores?
Glycogen storage disorders (Von Gierke's)
Galactossaemia
Fatty acid oxidation disorders (MCADD)
110
Give examples of metabolic conditions with large molecule synthesis problems?
Peroxisomal disorders
| Glycosylation disorders
111
Give examples of metabolic conditions with defects in large molecule metabolism?
Lysosomal disorders e.g. Tay Sachs disease
112
Give examples of metabolic mitochondrial conditions?
MELAS
Kearn's
Sayre
POEMS
113
What are the key features of organic acidaemias?
High urea + ketones
Metabolic acidosis
Funny smells
114
How do you treat organic acidaemias?
Low protein diet, acylcarnitine + haemofiltration
115
What are the key features of urea cycle disorders?
High ammonia leading to encephalopathy + developmental delay
Resp alkalosis
Vomiting
?Diarrhoea
116
How do you treat urea cycle disorders?
Low protein diet- stops urea formation
117
What are the key features of aminoacidopathies?
```
High phenylalanine
Blue eyes
Fair hair/skin
Retardation
MSUD- sweaty feet
```
118
What are the key features of glycogen storage disorders?
Hypoglycaemia + lactic acidosis
Hepatomegaly
Developmental delay
Hepatoblastoma risk
119
How do you treat glycogen storage disorders?
Regular CHO
120
Key features of galactossaemia?
Increased Gal-1 phosphate levels cause cataracts
Hypoglycaemia
Neonatal jaundice
121
How do you treat galactossaemia?
Treat with low lactose/galactose
122
Key features of fatty acid oxidation disorders?
Hypoglycaemia
Cardiomyopathy
Rhabdomyolysis
Low ketones
123
How do you treat fatty acid oxidation disorders?
Regular carbs
124
What are the key features of peroxisomal disorders?
```
Poor feeds
Seizures
Retinopathy
Hepatomegaly
Mixed hyperbiliribinaemia
```
125
How do you screen for glycosylation disorders?
Measure serum transferrins
126
What are the key features of lysosomal disorders?
Very slow progress
Neuroregression
Hepatomegaly
Cardiomyopathy
127
How do you test for lysosomal disorders?
Test urine mucooligopolysaccharides + WBC enzyme levels
128
How is DM diagnosed?
Typical symptoms plus one of fasting glucose >7, OGTT >11.1 or random glucose>11.1, or without symptoms but with 2 of the above tests
NICE also recommends you use HbA1C>48
129
What is the definition of impaired glucose tolerance?
Random or OGTT >7.8 but <11.1
130
What is the definition of impaired fasting glucose?
Fasting glucose >6.1 but <7
131
In which type of DM are DKA more common?
Type 1
132
In which type of DM are hyperosmolar hyperglycaemic state (HHS) more common?
Type 2
133
What are the HHS criteria?
pH >7.3
Osmolarity >320mOsm
Blood Glucose > 30mM
Develops over few dats
134
What are the DKA criteria?
pH<7.3
Plasma glucose >11mM
Blood ketones >3mM
DKA- rapid
135
What are causes of hyperinsulinaemic hypoglycaemia?
Iatrogenic insulin
Sulfonylurea excess
Insulinoma
136
What are causes of hypoinsulinaemic hypoglycaemia?
+ve ketones- alcohol binge, no food, pituitary insufficiency, Addison's, liver failure
-ve ketones- Non-pancreatic neoplasms- fibrosarcomata, fibromata
137
What would you see in blood tests for non-islet tumour hypoglycaemia?
Low glucose, insulin, C-peptide, FFA and ketones
138
What causes non-islet tumour hypoglycaemia?
Tumour causes paraneoplastic syndrome secreting big IGF-2 which binds to IGF-1 and insulin receptors
139
What common problems originate from low birth weight?
```
Respiratory distress syndrome
Retinopathy of prematurity
Intraventricular haemorrhage
Patent ductus arteriosus
Necrotising enterocolitis (inflammation of bowel wall)- necrosis and perforation
```
140
Why does renal function differ in babies compared to adults?
Functional maturity only at 2yo
Low GFR for SA
Less reabsorption due to short proximal tubule
Reduced concentrating ability due to short loops of Henle + DCTs
Persistent sodium loss due to distal tubule being aldosterone insensitive
141
Why is there high insensible water loss in babies compared to adults?
High SA:BW ratio
Skin blood flow is increased
Metabolic/respiratory rate is higher than adults
Transepidermal fluid loss (skin not the best barrier)
However hypernatraemia common in first 2w of life
142
What would you suspect with jaundice within first 24h of life?
Acute haemolysis or sepsis
143
What would you suspect with jaundice after 2wks of life?
Hepatobiliary failure
144
What is normal GFR?
120ml/hr
145
What is renal clearance defined as?
Volume of plasma that can be completely cleared of a marker substance in a unit of time
146
What is the gold standard measure of GFR?
Inulin
147
What is the problem with the use of inulin?
It requires steady state infusion and it is difficult to assay so reserved for research
148
Which measure is used in clinical practice to measure renal function?
Creatinine- an endogenous marker
149
What is the problem with the use of creatinine?
Very variable between individuals and muscular ppl have high creatinine
150
What is the definition of an AKI?
A rise in serum creatinine over 26.5 in 48h or to 1.5x baseline in 48h
Can also be defined as urine output of less than 0.5ml/kg/hr
151
What are the different causes of AKI?
Pre-renal- reduced renal perfusion with no structural abnormality
Renal- vascular, glomerular, tubular, interstitial
Post-renal- characterised by obstruction to urinary flow
152
What emergency indications are there for dialysis?
```
Pulmonary oedema
Refractory hyperkalaemia
Metabolic acidosis
Uraemic encephalopathy
Drug toxicity e.g. lithium
```
153
5 stages of CKD?
```
1- kidney damage with GFR>90
2- mild decrease in GFR 60-89
3- Moderate decrease in GFR 30-59
4- Severe decrease in GFR 15-29
5- End stage <15 or dialysis
```
154
Commonest causes of CKD?
```
Diabetes
Atherosclerotic renal disease
HTN
Chronic glomerulonephritis
Infective or obstructive uropathy
PKD
```
155
What are the 4 main consequences of CKD?
1. Progressive loss of homeostatic function- acidosis + hyperkalaemia
2. Progressive failure of hormonal function- anaemia (loss of EPO synthesis) + Renal bone disease (2' hyperparathyroidism due to low vit D)
3. CVD- vascular calcification + atherosclerosis and uraemic cardiomyopathy
4. Uraemia and death
