Chemical Pathology Flashcards
1
Q
What is normal concentration of H+
A
35-45nmol/L in ECF
pH= inverse log concentration of H+
2
Q
How is H+ buffered
A
Bicarbonate is a weak acid which mops up H+ in the short term- long term the kidney needs to excrete H+ and regenerate bicarbonate ions
3
Q
How is H+ buffered in RBC
A
Using haemoglobin
4
Q
Main buffering equation
A
H+ + HCO3-= H2CO2 + H20
5
Q
What principles causes a metabolic acidosis and examples
A
Increased H+ production- DKA
Decreased H+ excretion- renal tubular acidosis
Loss of bicarb- intestinal fistula
6
Q
What do lungs do in metabolic acidosis
A
Hyperventilate to shift equation
7
Q
What will see in compensated metabolic acidosis
A
Drop in CO2 with a compensated H+
8
Q
How does body compensate for respiratory alkalosis
A
Will try to increase regeneration of bicarb- harder and slower to compensate metabolically so short term will not see increase in bicarb
9
Q
What causes metabolic alkalosis
A
Increased H+ excretion
Can be potassium excretion too
Ingestion of bicarb
10
Q
How is metabolic alkalosis compensated for
A
Hypoventilate
11
Q
What causes respiratory alkalosis
A
Hyperventiation- panic attack, salicylates stimulate the brainstem early
12
Q
What causes a loss of bicarb
A
Diarrhoea
High output stoma
Pancreatic fistula
13
Q
What causes an increase in H+ production
A
DKA
Lactate
Ethylene glycol
Aspirin OD
Metformin
Uraemia
14
Q
What causes a reduction in H+excretion
A
Addisons
Renal failure- renal tubular acidosis
15
Q
What causes a metabolic alkalosis
A
Hypokalaemia
H+ loss from vomiting
Bicarbonate ingestion
16
Q
What do you get in an aspirin overdose
A
Can get mixed respiratory alkalosis and metabolic acidosis
Metabolic alkalosis as stimulates resp centre
Increases excretion of bicarb
17
Q
What are causes of addisons
A
TB
Autoimmune
Metastases
Adrenal haemorrhage
Amyloidosis
18
Q
What causes adrenal haemorrhages
A
Meningococcal infections- waterhouse friederichsen syndrome
19
Q
Blood findings of addisons
A
Low sodium
High K
Low glucose
20
Q
Signs on examination of addisons
A
Skin pigmentation
Postural drop in BP
21
Q
Test for addisons
A
Short synacthen test
Measure cortisol and ACTH then administer ACTH
Check the cortisol and 30 and 60 mins
22
Q
Managmeent of addisons
A
Hydrocortisone/fludrocortisone if primary addisons
23
Q
Presentation of conns
A
Uncontrollable HTN
High Na
Low K
24
Q
Investigation for conns
A
Plasma aldosterone:renin ratio will be higher
25
Managment for conns
Spironolactone-
Surgery if indicated
26
Presentation of phaeos
Severe transient hypertension
Arrythmias
27
Treatment of phaeos
Alpha blockade
Beta blockade
Surgery when BP controlled
28
Investigations for phaeos
Plasma and urinary 24 hour metanephrines/catecholamines/Vanillylmandelic acid (VMA)
Metanephrines are breakdown product
VMA in final synthesis step
29
How are inherited metabolic disorders screened for in the UK
Guthrie blood spot test on heel at 6 days old
30
What metabolic diseases are screened for in guthrie blood spot test
Congenital hypothyroidism
Cystic fibrosis
Thalassaemias and haemoglobinopathies
Metabolic disorders
- isovalaeric acidaemia
- maple syrup disease
- PKU
- homocysteinuria
- MCADD
- glutaric aciduria type 1
31
What is the defect of phenylketonuria
Phenylanine hydroxylase deficiency which converts phenylalanine to tyrosine
32
What is screened for in phenylketonuria
Phenylalanine in the blood
33
What 2 metbaolites other than phenylalanine are raised in phenylketonuria and where
Phenylpyruvate in the blood
Phenylacetic acid in the urine
34
How is phenylketonuria treated
Phenylalanine replacement and amino acid supplements
Must be started in first 6 weeks of life
35
What is screened for in congenital hypothyroidism
TSH levels
36
What is screened for in CF
Immune reactive trypsin- must be above 99.5th centil 3 times
If positive then do genetics
37
What is MCAD and the pathophysiology
Medium chain acylCoA dehyodrogenase deficiency
Involved in fatty acid breakdown for glucose sparing metabolism
38
What is screened for in MCAD
Acylcartinine by tandem Mass spectometry
39
Triad for phenylketonuria
Mental retardation
Blonde hair
Blue eyes
40
Triad for homocysteinuria
Lens dislocation
Mental retardation
Thromboembolism
41
What do urea cycle disorders present with
Resp alkalosis
Vomiting (not diarrhoea)
Neuro encephalopathy
Dietary avoidance of things
42
How do you treat hyperammonaemia
Low protein diet
43
What is blood finding of urea cycle disorder
High ammonia as urea not being formed
Resp alkalosis
44
What are organic acidurias
A group of inherited metabolic disorders where acidic metabolites accrue in the blood/urine
45
What causes cheesy or sweaty smelling urine
Isovalaeric acidaemia
46
How do organic acidurias present
Depends on if neonate or later on
Neonates
- Unusual odour
- Truncal hypotonia
- Limb hypertonia
- Hyperammonaemia with metabolic acidosis high AG
Chronic intermitten form
- recurrent episodes of ketoacidosis, cerebral abnormalities
- Reye syndrome
47
What is Reye syndrome
Vomiting
Lethargy
Increased confusion
Resp arrest
48
What are triggers for Reye syndrome
Salicylates
Anti-emetics
Valproate
49
What is done in screen for Reye syndrome
Ammonia
Amino acids in blood and urine
Urine organic acids
Glucose and lactate
Blood spot carnitine
50
What is blood finding of MCAD
Hypoketotic hypoglycaemia as shows cant break down fats
51
Clinical associations of MCAD
Hepatomegaly
Cardiomyopathy
52
How is MCAD treated
Regular carbohydrates
53
What is galactosaemia
A disorder of galactose metabolism where Gal-1-put is mutated leading to elevated levels of Gal-1-phosphate which causes kidney and liver disease
54
What is main pathological finding in galactossaemia
High neonatel conjugated bilirubin
55
Presentation of galactossaemia
Hypoglycaemia
Jaundice
Severe vomiting
Cataracts
Recurrent E coli infections
56
How to treat galactossaemia
Low galactose diet
57
What is Von gerkes disease
Glycogen storage disorder where cant break down glycogen so liver accumulates glycogen
58
Blood findings of von gierkes disease
Hypoglycaemia
Lactic acidosis
Neutropenia
59
Examination finding of von gierkes
Hepatomegaly
Nephromegaly
60
How are mitochondrial disorders diagnosed
Muscle biopsy
61
Which is predominant transporter of cholesterol in fasted state
LDL
62
Where does cholesterol come from in GI tract
Diet
Bile
63
Where are bile acids absorbed
Terminal ileum
64
Where is cholesterol absorbed
Jejunum
65
What is major transporter of triglycerides in fasting state
VLDL
66
Genes involved in FH
Dominant mutations of LDLR, APOB, PCSK9
Rarely get autosomal recessive-LDLRAP1
67
What are causes of primary hypercholesterolaemia
FH
Polygenic hypercholesterolaemia
Familial hyper alpha lipoproteinaemia
Phytosterolaemia
68
What is phenotype of familial hyper alpha lipoproteinaemia
Deficiency of CETP which results in high HDL- beneficial
69
Mutations seen in phytosterolaemia
ABC G5 and G8
These are proteins which prevent cholesterol absorption in the jejunum
If mutated get
70
What is function of PCSK9
Binds to LDLR and promotes degradation
Gain of function mutations cause FH
Loss of function are protective against CVD
71
What causes primary hypertriglyceridaemia
Familial type 1
Familial type V
Familial type IV
72
What causes familail type I hypertriglyceridaemia
Lipoprotein lipase or apoC II deficiency
73
What causes familail type IV hypertriglyceridaemia
increased synthesis of TG
74
What causes familail type V hypertriglyceridaemia
apoA V deficiency
75
Causes of primary mixed hyperlipidaemias
Familial combined hyperlipidaemia
Familial dys-beta-lipidaemia Type III
Familial hepatic lipase deficiency
76
What causes Familial dys-beta-lipidaemia Type III
Aberrant Apo E/2
77
What disease is famial dys-beta-lipidaemia assoicated with a risk of
Alzheimers
78
Pathognomic sign of Familial dys-beta-lipidaemia Type III
Yellow palmar crease (palmar striae)
79
Secondary causes of hyperlipidaemia
Exogenous sex hormones
Hypothyroidism
Prengnacy
Nephrotic syndrome
Obstructive liver disease
80
What are causes of hypolipidaemia
Abeta-lipoproteinaemia
HypoBeta-lipoproteinaemia
Tangier disease
Hypo-alpha lipoproteinaemia
81
Pathophysiology of Abeta-lipoproteinaemia
MTP deficiency
82
Pathophysiology of HypoBeta-lipoproteinaemia
Truncated apoB protein
83
Pathophysiology of Tangier disease
HDL deficiency
84
Pathophysiology of Hypo-alpha lipoproteinaemia
ApoA-I mutations
85
Best drug for reducing TG
Fibrates
86
Treatment for reducing high lipoprotein a
Nicotinic acid
87
MOA of statin
HMG-CoA reductase inhibitor
Reduces liver cholesterol synthetic function
88
Treatment for obesity
First line hypocaloric conservative
Medical- orlistat
Bariatric surgery, BMI>35
89
What other drug has been trialled for obesity but was disconitnued and why
Rimonabant- cannabinoid antagonist
Increased risk of suicide
90
What are 4 fat soluble vitamins and where stored
ADEK
Adipose
91
Where are water soluble vitamins stored
Theyre not
In blood and pass through to urine
92
What is name for vit B1
Thiamine
93
What is name for vit B2
Riboflavin
94
What is name for Vit B6
Pyridoxine
95
What is name for vit B12
Cobalamine
96
What is deficiency of vit B1
Beri Beri
Wernickes
Neuropathy
97
Test for vit B1
RBC transketolase
98
Deficiency of Vit B2
Glossitis
Corneal ulceration
99
Test for B2
RBC glutathione reductase
100
Test for vit B6
RBC AST activation
101
Name for Vit C
Ascorbate
102
Vit C deficiency
Scurvy- bleeding gums, teeth can fall out, joint pain, low mood
103
B6 deficiency
Skin changes
Sideroblastic anaemia
104
B6 excess
Neuropathy
105
Vit C excess
Renal stones
106
What is B3
Niacin
107
Niacin deficiency
Pellagra- 3ds
Diarrhoea
Dementia
Dermatitis
108
Test for B12
Serum B12
109
Test for folate
RBC folate
110
Test for Vit C
Plasma vit C
111
Tests for iron
FBC
Serum Fe
Ferritin
112
Iodine deficiency
Goitre
Hypothyroidism
113
Name for vit A
- deficiency
- excess
- test
Retinol
Colour blindess
Hepatitis and exfoliation
Serum level
114
Name for vit D
- deficiency
- excess
- test
Cholecalciferol
- rickets or osteomalacia
- hypercalcaemia
- serum
115
Name for vitamin E
- deficiency
- test
Tocopherol
- anaemia, neuropathy, IHD risk later in life
- serum level
116
Name for vitamin K
- deficiency
- test
Phytomenadione
- defective clotting
- PTT
117
Zinc deficiency
Dermatitis
118
Copper deficiency
- excess
- test
Anaemia- as body absorbs less iron and osteoporosis
Wilsons
Cu and caeruplasmin
119
Fluoride deficiency
- excess
Dental caries
- flurosis white and borwn speckles on your teeth
120
What is best way to determine obesity in a clinical setting
Waist hip ratio- good for predicting adiposity and CHD risk
BMI affected by things such as race and muscle mass
121
What is cut off BMI for obesity
30
Minus 2.5 for south asia
122
What is marasmus
Deficiency in all macronutrients
- shrivelled
- retarded growth
- mscle wasting
- no subcut fat
123
What is kwashiorkor
Lack of protein where become oedematous
124
When do babies reach functional maturity of GFR
2 years
- babies born prior to 36 weeks wont have a full complement of nephrons
125
How do babies compare to adults in terms of total body water
Adults are 60%
Neonates 75%
Even higher in preterm (85%)
This is why babies lose weight in the first week of life
126
Why do neonates lose so much water
High surface are to body weight
Increased skin blood flow
Metabolic respiratory rate is higher than adults
Transepidermal fluid loss as skin isnt properly keratinised yet
127
How does CAH present in neonates
Addisonian crisis
Hypoglycaemia
128
What metabolite is raised in CAH
17-OH-progesterone
129
How is calcium transported in the blood
50% free
40% bound to albumin
10% to phosphate
130
How does PTH gland respond to hypocalcaemia
Increases calcium reabsorption in the kidney
Increases tubular hydroxylation of Vitamin D
Mobilises calcium from bone
131
How does PTH affect phosphate
Increases excretion of phosphate in kidney
132
What is difference between Vit D2 and D3
D2 is a plant vitamin
D3 is an animal synthesised
Both active
133
What is the stored and measured form of vitamin D
25-hydroxy-vitamin D
134
Actions of calcitriol
Intestinal calcium and phosphate absorption
Bone resorption
Other actions- immune gene control therefore get deficiency associations with cancers and autoimmune disease
135
Risk factors for Vitamin D deficiency
Lack of sunlight
Dark skin
Diet
Malabsorption
136
What do you get in osteomalacia
Bone and muscle pain
Looser zones
137
What are looser zones
Pseudo fractures
138
Blood findings of Vit D deficiency
Low Ca and Po
Raised PTH and ALP
Low Vit D
139
Presentation of rickets
Bowed legs
Costochondral swelling
Widened epiphyseal areas wrists
Myopathy
140
Causes of osteomalacia
Renal failure
Anticonvulstants can cause vit D
Lack of sunlight
Chappatis (phytic acid high levels)
141
Why get high ALP in osteomalacia
PTH gets raised which causes in excess bone resorption
142
Classic fractures seen in osteoporosis
Colles fracture
Neck of femur
Vertebra
143
How is osteoporosis diagnosed
Using DEXA scan of wrist, lumbar spine and neck of femur
T score less than -2.5
Osteopenia between -1 and -2.5
144
What is T score vs Z score
T= healthy person comparison
Z= age matched control
145
What is the Z score used for
To idnetify bone loss in younger patinets
146
Risk factors for osteoporosis
Childhood illness
Low Vit D
Early menopause
Long term steroids/ cushnigs, hyperprolactinaemia, thyrotoxicosis
Smoking
Alcohol
147
Treatment for osteoporosis
Lifestyle
- smoking and alcohol
- weight bearing alcohol
Drugs
- Vit D
- alendronate
- PTH analogue
- oestrogen
- SERM (raloxifene)
148
What is alendronate
- side effect
Bisphophonate
- side effect= gastric irritation and so is low compliance
149
What is example of PTH analogue
Teriparatide
150
What should PTH be in hypercalcaemia
Zero
151
Questions when get hypercalcaemia
Is it an anomaly- repeat test
Check PTH
If suppressed most likely cancer- then sarcoid etc
If high then hyperparathyroidism
152
Causes of hypercalcaemia
Hyperparathyroidism- most common in young healthy and community
Cancer- most common in old and ill, in secondary care
Vit D excess
Sarcoid
Milk alkali
153
Most common cause of hypercalcaemia
Primary parathyroidism
154
Causes of primary hyperparathyroidism in order of likelihood
Single adenoma
Hyperplasia
Multiple adenomas- association with MEN1
Carcinoma
155
Which bone most commonly affected in primary hyperparathyroidism
Wrist- get colles fracture
156
What causes Familial hypocalcuric/benign Hypercalcaemia
Mutation in Calcium sensing receptor which means doesnt excrete PTH as early as should
Have mild hypercalcaemia naturally
157
3 types of malignant hypercalcaemia
PTHrP from small cell lung cancer
Bone metastases
Haematological malignancy
158
How does myeloma cause hypercalcaemia
Cytokines produced not infiltration
159
What can causes excess vitamin D
Sunbeds
Too many tablets
160
Treatment of hypercalcaemia
Fluids- normal saline as much as can give 4L daily
Bisphosphonates- if cause known to be cancer
Treat cause
161
When is only time can give bisphosophonates in hypercalcaemia
If cancer is known to be cause
162
Signs and symptoms of hypocalcaemia
Chvostek- tap face
Trousseau- BP cuff
Hyperrreflexia
Stridor
Convulsions
163
ECG finding of hypocalcaemia
Prolonged QT
164
Non PTH driven causes of hypocalcaemia
Vit D deficiency
CKD
PTH resistance
165
PTH driven causes of hypocalcaemia
Post surgical
Radiation
Mg deficiency
Auto-immune hypoparathyroidism
166
What causes secondary hyperparathyroidism
CKD
Vit D deficiency
167
Tertiary hyperparathyroidism causes
Prolonged secondary- mainly from dialysis
Renal transplant
168
Symptoms of pagets disease
Focal pain
Warmth
Deformity
Fracture
169
Complications of pagets
HF
Increased risk of malignancy
170
Treatment of pagets
Bisphosphonates
171
Investigations for pagets
ALP
Nuclear scan/XR
172
What causes renal osteodystrophy
Secondary hyperparathyroidism
Aluminium retained from CKD
173
How does evolocumab affect prognosis in patients with known cardiovascular disease
Reduces incidence of events but not mortality
BUT....
Absolute risk reduction very small and very expensive to do so
174
Who should evolocumab only be used in
Statin intolerant
Uncontrolled lipids like FH
175
What is the legacy effect
Benefits persist from early intervention in glucose control
If have tight control later in disease course in those with established CVD disease can increase mortality
176
What are the important physiological effects of SGLT2i
Reduce glucose, weight, waist circumfrence and BP
177
What endocrine condition can be seen alongside addisons
Primary Hypothyroidism
Due to concurrent autoimmune conditions
178
Example of alpha blockade
Phenoxybenzamine
179
1st line investigation for cushings
24 hour urinary cortisol
Overnight dexamethasone suppression test
180
Presentation of cushings
Moon face
Buffalo hump
Striae
Acne
HTN
DM
Proximal myopathy
Hirsutism
181
What is only aetiology which causes cushings disease
Pituitary tumours
182
Causes of cushings
ACTH dependant- pituitary tumour, ectopic ACTH production
ACTH independent- adrenal adenoma, adrenal nodular hyperplasia, iatrogenic steroids
183
Which tumours can cause cushings
Small cell lung cancer
Carcinoid tumour
184
Most common cause of cusings syndrome
Iatrogenic steroids
185
Most common electrolte abnormality
Hyponatraemia
186
how is water balance controlled
ADH increasing aquaporin insertion in collecting duct via V2
187
Where are V1 receptors for vasopressin
Vascular smooth muscle increasing vascular constriction
Only at high concentrations of vasopressin
188
2 main stimuli for ADH release
Serum osmolality- hypothalamic osmoreceptors-> drives thirst
Blood pressure- baroreceptors in carotid and aorta
189
First thing assess when patient has hyponatraemia
Volume statuts
190
What is most useful clinical sign of hypovolaemia
Low urine Na+
191
Which drugs make interpreting urinary sodium difficult
Diuretics
192
Hypovolaemic cause of hyponatraemia
Diarrhoea
Vomiting
Diruretics
Salt losing nephropathy
193
Euvolaemiac causes of hypontraemia
SIADH
Addisons
Hypothyroidism
194
Causes of hypervolaemiac hyponatraemia
Liver, renal and cardiac failure
195
What causes hypervolaemia in cirrhosis
Excess NO which is a vasodilator as should be filtered by liver
196
Causes of SIADH
Lung pathology
CNS pathology
Drugs- SSRIs, opiates, TCA, PPIs, carbamezapine
Tumours
Surgery
197
Investigations for euvolaemiac hyponatraemia
TFTs, short synacthen, plasma and urine osmolality
198
Plasma and urine osmolality in SIADH
Low plasma
High urine
199
How to diagnose SIADH
Rule out hypovolaemia, hypothyroidism and addisons
Reduced plasma osmolality
Urine osmolality over 100
200
How to manage a hypovolaemic hyponatraemic patient
Volume replacement with 0.9% saline
201
How to treat hypervolaemic hyponatraemia
Fluid restriction
Treat underlying cause
202
How to treat euvolaemic hyponatraemia
Fluid restriction
Treat underlying cause
203
What can result from severe hyponatraemia
Reduced GCS
Seizures
204
How to treat severe hyponatraemia
Seek expert help only with hypertonic 3% saline
Only when reduced GCS and seizures
205
If fluid restriction isnt useful in treating hyponatraemia what can give
Demeclocycline- reduces responsiveness of collecting duct to ADH
Tolvaptan- V2 antagonist
206
What causes hypernatraemia
Unreplaced water loss
- GI and sweat losses
- diabetes insipidus
Poor intake of water seen in elderly and children
207
What investigations for patients with suspected diabetes insipidus
Serum glucose, potassium and calcium (to exclude DM, hypokalaemia and hyperkalaemia as all cause excess water loss)
Plasma and urinary osmolality
Fluid deprviation test
208
Treatment for hypernatraemia
Fluid with 5% dextrose to correct water deficit
0.9% saline to replace ECF volume loss
Sodium mesurements every 5 hours
209
How can DM affect serum sodium
Very variable
Draws water out of cells causing hypernatraemia
Osmotic diuresis causing loss of water and hypernatraemia
210
Which electrolyte imbalance can lead to depression
Hypercalcaemia
211
Difference between smiths and colles fracture
Smiths- fallen on flexors of hands
Colles- fall with hands out on extensors
212
Complications of hypercalcaemia
Renal stones
Pancreatitis
Peptic ulcer disease
Skeletal changes/fractures
Osteitis fibrosa cystica
213
Sign on examination of hypercalcaemia
Band keratopathy- corneal degeneration
214
What is late complication of hypercalcemia
Osteitis fibrosa cystica- bone remodelling and weakening
215
Interesting feature of sarcoid hypercalcaemia
Is seasonal- is increased in summer
216
Factors which contribute to whether clearance = eGFR
Not bound to serum proteins
Freely filtered and not secreted or reabsorbed
217
What is gold standard for eGFR
Ready state infusion of Inulin but mainly used in research
218
What is normal GFR rate and the normal age related decline rate
120ml/hr
1ml/hr/ year as age
219
What posioning can lead to calcium oxalate stones
Ethylene glycol
220
Grade 1-3 AKI creatinine
Stage 1- increase in 26 or by 1.5-1.9 from reference creatinine
Stage 2- increase in 2.0 to 2.9
Stage 3 increase in over 3.0
221
Causes of pre-renal AKI
Reduced circulating fluid perfusion or specific to kidney ie renal artery stenosis
222
Which drugs predispose to pre renal AKI
NSAIDS
Calcineurin inhibitiros
Diuretics
223
How do NSAIDS and calcinruin inhibitors cause pre renal AKI
Reduce afferent arteriole pressure
224
Causes of renal AKI
Vascular disease- vasculitides
Acute glomerulonephritis
Tubular injuries
Infiltration- lymphoma, myeloma, amyloidosis
Thrombotic glomerulonephritis
225
What causes direct tubular injury
Ischaemia
Endogenous toxins- light chain in myeloma, myoglobin
Exogenous- aminoglycosides, aciclovir, contrast
226
What is most common cause of acute renal failure
Acute tubular necrosis
227
Causes of post renal AKI
Blocked catheter
BPH
Stones
Bladder/prostate cancers
228
Effects of prolonged obstructive uropathy
Glomerula ischaemia
Interstitial scarring
Tubular damage
229
What are used to measure severity of AKI
Urine output or creatinine
230
CKD stages
1. GFR over 90
2. GFR 60-89
3. 30-59
4. 15-29
5. less than 15
231
Most common causes of CKD
DM
Glomerulonephritis
HTN/atherosclerosis
Reflux nephropathy
PCKD
232
Causes of hyperkalaemia in CKD
Spironolactone
ACEi
Eating foods like chocolate, dried fruits and tomatoes
233
Problem of hyperkalaemia in CKD
Tachyarrythmias which can become VT
234
Anaemia in CKD
Normochromic normocytic anaemia
Seen in GFR less than 30
235
What is used to treat CKD anaemia
EPO stimulating agents like darbapoetin
236
Cardiac complications of CKD
Uraemiac cardiomyopathy with 3 phases
LVH->LV dilation->LV failure
237
Vascular complications of CKD
Calcified vessels which leads to increased CVD risk
238
Preferred sample for post mortem blood analysis
Post mortem femoral vein as allows for screening and quantitation
239
How to calculate anion gap
Na+K-Cl-bicarb
240
What causes itching in liver disease
MUST BE OBSTRUCTIVE JAUNDICE
Caused by bile salts
241
What is Km (michaelis-menten)
Substrate concentration at which reaction velocity is at 50% of maximum
242
Where is ALP found and what causes it to be raised
Liver- Cholestatic disease
Bone- fracture, pagets, osteomalacia, rickets, cancer, hyperparathyroidism, renal osteodystrophy
Placenta- pregnancy in last trimester, germ-cell tumour
Intestine- none
243
Where is AST versus ALT more prevalent
AST- heart
ALT- liver
ALT mores specific for liver disease
244
Where are AST and ALT found
Liver
Heart
Muscle
Kidney
Pancreas
245
Where is GGT found and what can increase itt
Hepatobiliary
Pancreas
Kidney
Diseases of these
Certain
246
What drugs can induce GGT
Alcohol
Rifampicin
Barbiturates
247
Where is LDH found and what raises it
WBC- lymphoma
RBC- haemolysis
Placenta- seminoma
Skeletal muscle- myositis
Liver- any injury
Heart- any cell death
248
Where is amylase found
Pancreas- bowel obstruction, perf duodenal ulcer, bowel obstruction
Salivary gland- stones, infection like mumps
249
What is macro-amylase
Amylase bound to immunoglobulin which can cause confusion
250
Where is CK found and what raises it
Muscle- myositis, strenuous exercise, myopathy, rhabdomyolysis
Cardaic- any injury
*higher in afrocarribeans*
251
When does troponin I begin to rise post injury
2 hours
252
How is troponin measured post MI
Measured then measure again hour later
Look for over 50% rise
253
In heart failure what cardiac marker is measured
NT Pro-BNP
NOT BNP as short life too short
254
Management of hypoglycaemia in adults if alert and oriented
For rapid acting- juice and sweets
For longer acting sanwich
255
Management of hypoglycaemia if drowsy and confused but swallow intact
Buccal glucose- hypostop or glucogel
256
Management of hypoglycaemia if unconscious or concerned not able to swallow
IV access and 20% glucose through
257
What use if hypoglycaemia patient deteriorating, treatment refractory, insulin induced or difficult IV access
IM glucagon 1mg
258
Response of body to hypoglycaemia
1. Suppress insulin
2. Increased glucagon
3. Sympathetic activation
4. Cortisol, ACTH and GH all released
259
What are counter regulation responses to hypoglycaemia
Increased glucose
Low insulin and c-peptide
Beta oxidation increases free fatty acids and ketone production
260
Venous versus capillary blood glucose measurements in hypoglycaemia
Venous collected with fluoride oxalate preservative whereas CGB point of care analyser
Venous is gold standard as better precision with low glucose
261
Causes of hypoglycaemia in non diabetic
Fasting
Very unwell
Hyperinsulinism
Post gastric bypass
Drugs- eta blocker, salicylates, alcohol
Extremely low BMI
Factitious
262
Causes of hypoglycaemia in diabetic
Medication
Missed meal/ low carb
Excessive alcohol
Strenuous exercise
Co-existing autoimmune conditions
263
How can hypoglycaemia be classified
Hypoinsulinaemic
Hyperinsulinaemia- then can be with low or high C-peptide
264
Hypoglycaemia with high insulin and low c peptide
Factitious insulin
265
Main differentials for hyperinsulinaemic hypoglycaemia with high c peptide
Islet cell tumour- insulinoma
Sulphonylurea toxicity
Differentiate by doing urinary/serum drug screen
266
What presents with hypoglycaemia, low insulin and low cpeptide, low FFA and ketones
Paraneoplastic syndrome where produce big IGF2 which binds to IGF-1 receptor and insulin receptor
267
Which tumours do you get non-islet cell tumour hypoglycaemia in
Mesenchymal- mesothelioma and fibroblastoma
Occsaionally carcinomas
Production of big IGF2
268
What is autoimmune insulin syndrome
Where get abs directed against insulin typically triggered by drugs or infections
Very common in japan
269
What can cause hypoglycaemia after eating a meal
Post gastric bypass
Hereditary fructose intolerance
Early DM
270
What are definitions of DM
Fasting glucose over 7mm
Glucose tolerance test over 11
HbA1c over 48mmol
271
How can non functioning pituitary adenoma cause hyperprolactin
They can press on stalk which prevents dopamine travelling to APH
272
What is main difference between blood gas in acute vesus chronic resp acidosis
Acute- increased CO2 leading to increase in H+ and bicarb
Chronic- H+ may return to normal however bicarb will remain high with Co2
273
Why does hypokalaemia cause metabolic alkalosis
To retain potassium the kidney retains more sodium at expense of H+
274
What are the 3 main mitochondrial disorders
Presents at birth
- Barth (cardiomyopathy, neutropenia and myopathy)
Presents 5-15
- MELAS ( mitochondrial encephalopathy, lctic acids and stroke like episodes)
Presents 12-30
- Kearns- Sayre (Chronic progressive external opthalmoplegia, retinopathy, deafness, ataxia)
275
Presentation of osteopenia of prematurity
Cupping of long bones
Easy fractures
Extremely high ALP
276
How is osteopenia of prematurity treated
With calcium and phosophate supplements
277
What are the different types of vitamin D
Vitamin D2- ergocalciferol the plant one
Vitamin D3- cholecalciferol
Calcitriol
278
What is corrected calcium
Accounts for that bound to albumin
Corrected calcium= serum calcium+0.02*(40-serum albumin)
279
Describe the synthesis of Vitamin D
In the skin 7 dehydrocholesterol is converted to cholecalciferol (Vitamin D3)
Liver converts to 25 hydroxycholecalciferol
Kidney converts to 1,25-dihydroxycalciferol (calcitriol)
280
Other than cancer what can cause non-PTH driven hypercalcaemia
Sarcoidosis (non-renal 1α hydroxylation)
Thyrotoxicosis (thyroxine -> bone resorption)
Hypoadrenalism (renal Ca2+ transport)
Thiazide diuretics (renal Ca2+ transport)
Excess vitamin D (eg sunbeds…)
281
Qujestions when get hypocalcaemia
Is it a genuine result- repeat and adjust for albumin
What is PTH?
282
High TSH
Low T4
Low glucose
Hyponatraemia
Hyperkalaemia
Schmidt syndrome- as hypothyroidism and addisons
283
How do pre renal akis respond to fluids
Restorative
BUT
If prolonged leads to ischaemia which causes ATN which does not respond
284
What are problems of acidosis from CKD
Failure to excrete protons
- muscle degradation
- osteopenia
- cardiac dysfunction
285
How is acidosis from CKD treated
Oral sodium bicarb
286
How much does hair grow in a month
1cm according to hair analysis
287
Describe RAAS system
Renin converts angtionensin from liver to angiotensin 1 peripherally
Angiotensin 1 converted in lung by ACE to angiotensin II which acts on adrenal
288
How does aldosterone increase K secretion
Increases number of open Na channels on luminal membrane
Increased Na reabsorption makes lumen electronegative and creates electrical gradient
K secreted into lumen
289
Causes of hyperkalaemia
Renal injury
Drugs- ACEi, ARBs, spironolactone, NSAIDS
Low aldosterone- T4 renal tubular acidosis, addisons
Release from cells in acidosis and rhabdomyolysis
290
ECG change of hyperkalaemia
Peaked T waves
291
Management of hyperkalaemia
10ml 10% calcium gluconate
50ml 50% dextrose with 10 units of insulin
Nebulised salbutamol
Treat cause
292
Causes of hypokalaemia
GI loss
Renal loss- excess cortisol and aldosterone, loop diuretics and thiazides, T1 and T2 renal tubular acidosis, Barter syndrome and gieltman syndrome
Redistrubtion to cells- insulin, salbutamol, alkalosis
293
What is difference of where barter and gieltman syndrome affect
Both cause hypokalaemia
Barter- loop of henle triple transporter
Gieltman- DCT
294
Presentation of hypokalaemia
Muscle weakness
Cardiac arryhmia
Polyuria and polydipsia
295
How is hypokalaemia treated
3-3.5
- oral potassium chloride tablets ( 2 sandok tablets)
- recheck levels
less than 3
- IV KCl max 10mmol/hour as irritant to veins
296
What is lesch-nyan disease
Get a deficiency in the enzyme HPGRT which leads to primary hyperuricaemia
297
Presentation of lesch-nyan disease
Developmenal delay at 6 months
Choreiform movements around 1 year
Self mutilation (bite lips and fingers)
Severe UMN disease
Mental retardation
298
Management of gout
NSAIDS
Colchicine
(Do not modift urate concentration)
299
How to manage hyperuricaemia
Drink lots of water
Allopurinol
300
Which patients is pseudogout normally seen in
Osteoarthritis
301
What are the hormones produced by the anterior pituitary
ACTH-> affected by CRH
TSH-> affected by TRH
LH > affected by LHRH
FSH-> affected by LHRH
GH -> affected by GHRH
Prolactin- affected by TRH and negatively from dopamine
302
How does combined pituitary testing work
Triple test
Must check heart beforehand and no epilepsy
Gain IV access for administration of IV 20% dextrose if needed
Fast overnight and give insulin, TRH and LHRH in combined syringe
Measure glucose, cortisol, TSH, thyroxine and prolactin every 30 mins
303
In pituitary failure which hormone replacement is needed most urgently
Hydrocortisone
304
Treatment of prolactinoma
Dopamine agonist- cabergoline or bromocriptine
Surgery if needed
304
What is the test for acromegaly
Glucose tolerance test
Can also measure IGF-1
305
Management of acromegaly
Surgery if needed
Octreotide- somatostain analogue
Cabergoline- dopamine agonist
306
What class of drug is octerotide
Somatostain analagoue which reduces GHRH released
307
What is a porphyria
Deficiency in enzymes of haem biosynthesis pathway
308
What is inheritance of hereditary coproporphyria and variegate porphyria
Autosomal dominant
309
What is the most common acute porphyria
AIP
310
What is the most common porphyria
Porphyria cutanea tarda
311
How do the non-acute porphyrias present
Skin lesions only- blistering, pigmentation, erosions
EPP- happens immediately after sun exposure
312
What is the only porphyria which presents in children
Erythopoietic protoporpyria
313
What is pathophysiology of porphyria cutanea
Uroporphyrinogen III decarboxylase deficiency (UROD)
Normally precipitated by liver diseases and alcohol use
314
Investigation for erythopoietic protoporphyria
RBC protoporphyrin levels
315
In acute porphyria most useful sample to send is
Urine
316
Causes of raised anion gap metabolic acidosis
MUDPLIES
Metformin
Uraemia
DKA
Paraldehyde
Iron
Lactate
Ethanol
Salicylate
317
In mixed resp and metabolic acidosis in a COPD patient what could be causing the metabolic acidosis
Uraemia
DM leading to ketones
Renal tubular acidosis
318
What are blood findings of tertiary hyperparathyroidism
High calcium
High PTH
High phosphate
319
What are blood and urine findings of diabetes insipidus
Hypernatraemia
Very low urinary osmolality
320
What are blood and urine findings of primary/secondary polydipsia
Hyponatraemia
Low urinary osmolality
321
What are urinary and plasma findings which suggest diabetes insipidus
Plasma osmolality:urine osmolality ratio over 2
Urine very dilute despite concentrated plasma
322
Treatment for cranial diabetes insipidus
Desmopressin
323
Treatment for nephrogenic diabetes insipidus
Thiazide diuretics
324
How does cranial diabetes insipidus react in water deprivation test
Urine osmolality responds to desmopressin by increasing over 600
325
How does nephrogenic diabetes insipidus react in water deprivation test
Urine osmolality to remain constant even after desmopressin
326
What are the 5 thyroid cancers in order of prevalence and invasiveness
Papillary
Follicular
Medullary
Anaplastic
Lymphoma
327
Thyroid cancer with psammoma bodies and orphan eyes on histology
Papillary
328
Which thyroid cancer produces calcitonin
Medullary
329
How is bilirubin conjugated
After breakdown from haem group forming unconjugated bilirubin get addition of glucuronyl group
330
How to interpret AST:ALT ratio
If above 1 then fibrosis
If above 2 very severe alcoholic disease
331
What do AST, ALT, ALP and GGT all stand for
Aspartate transaminase
Alanine transferase
Alkaline phosphatase
Gamma glutamyl transferase
332
If reject liver biopsy what can offer
Fibroscan which measures elasticity
333
Diagnostic test for gilberts
Fasting unconjugated bilirubin
334
Which antibiotic is best known for causing drug induced cholestasis
Augmentin- Co-amox
335
How to tell if liver disease acute
Preserved albumin synthetic liver function
336
What causes ALT of over 1000 in MI
Ishcaemic liver
337
Results of low dose dexamethasone test
Normal would be a low cortisol
High shows cushings of any cause
338
After low dose dexamethasone test/ 24 hour urinary cortisol what is next done investigation
Inferior petrosal sinus sampling
Used to be high dose dexamethasone test
339
How to interpret results of high dose dexamethasone test
If cortisol suppressed then suggests cushings disease
If remains high then either ectopic ACTH or adrenal cushings
If ACTH high then ectopic, if low then adrenal
340
Order of most common causes of non-iatrogenic cushings
Cushings disease 85%
Adrenal adenoma/hyperplasia 10%
Ectopic ACTH 5%
341
Causes of hyperthyoidism
Primary in order of prevalence
- Graves
- Toxic multinodular goitre
- Adenoma
Dequervains
Post partum thyroiditis
Molar pregnancy
342
Management options for hyperthyroidism
Carbimazole or propylthiouracil
Radio-iodine
Thyroidectomy
343
Dense firm thyroid
Riedels thyroiditis
344
Causes of hypothyroid
Iodine deficiency
Hashimotos
Dequervains
Drugs- lithium, amiodarone
Riedels thyroiditis
Post thyroidectomy
345
What is cancer marker for papillary and follicular thyroid cancer
Thyroglobulin
346
Histology of anaplastic thyroid cancer
Undifferentiated follicular, large pleomorphic giant cells,
spindle cells with sarcomatous appearance
347
Histology of medullary thyroid cancer
Amyloid sheets as calcitonin broken down into it
Dark cell sheets
348
Pathophysiology of CAH
Less alpha 21 hydroxylase which means no progression down pathway to cortisol and aldosterone
Get excess of progesterone
349
What does GH do
Increase glucose
Causes increase in insulin growth factor 1
350
What inhibits GH release
Somatostain
351
Blood findings of acromegaly
Hyperglycaemia
Prolactin
352
Causes of hyperglycaemia
DM
Post stroke
Pancreatitis
Cushings
Acromegaly
353
MOA of metformin
Increases sensitivity to insulin peripherally
Reduces hepatic gluconeogenesis
354
MOA of acarbose
Inhibits alpha glucosidase on brush border of small bowel
355
MOA of gliptins
Inhibits dipeptidyl dipeptidase IV which increases incretin
356
MOA of sulphonylureas
Increase insulin production from beta cells
357
MOA of empaglifizon
SGLT2 inhibitor which increases excretion of glucose
358
When can diagnose HHS
pH>7.3
Glucose over 30
Osmolarity over 320
359
Treatment of HHS
0.9% saline
Insulin only if ketones over 1
360
What does OGTT between 7.8 and 11.0 diagnose you with
Impaired glucose tolerance
361
What does fasting glucose 6.1 to 6.9 diagnose you with
Impaired fasting glucose
362
Where is bicarbonate reabsorbed
PCT
363
Which gives positive urine dipstick for blood other than erythrocytes
Myoglobin and haemoglobin
364
What is only drug that can increase bone density
Denosumab
365
MOA of cholestyramine
Binds to bile acids to prevent cholesterol reabsorption
366
What are brown tumours
Aggregations of osteoclasts caused by hyperparathyroidism
367
Histology of browns tumours
Multinucleate giant cells
368
How to calculate osmolar gap
2Na + glucose + urea
369
What trnasports cholesterol to liver
HDL
