Chemical Pathology Flashcards
(179 cards)
1
Q
3 main purines
A
adenosine
guanosine
inosime
2
Q
what enzyme is inactive in humans that leads to build up in urate?
A
uricase
3
Q
how are purines broken down? which enzyme?
A
purines –> hypo-xanthine –> xanthine –> urate (by xanthine oxidase)
4
Q
levels of urate in men and women
A
men: 0.12-0.42
women: 0.12-0.36
5
Q
what changes the solubility of urate?
A
decreases with temp and pH
6
Q
what is FEVA?
A
fractional excretion of uric acid
= 10%
only 10% of filtered urate in urine
7
Q
de novo purine synthesis pathway
when done?
rate limiting step?
A
- inefficient
- only done when high demand
- rate limiting step PAT
8
Q
what is the output of the de novo pathway?
A
IMP
AMP
GMP
9
Q
what is the salvage pathway?
A
predominant
energy efficient
scoops up partially catabolised purines
brings them to produce IMP/GMP
10
Q
main enzyme in salvage pathway
A
HPRT (aka HGPRT)
11
Q
what is the problem in Lesch-Nyhan? leads to?
A
absolute deficiency of HGPRT
X-linked
over drive of the de novo pathway = lots of IMP driven down catabolic pathway to produce urate
12
Q
symptoms of Lesch-Nyhan
A
normal at birth
developmental delay at 6 months
self mutilation
13
Q
causes of hyperuricaemia
A
increased production: secondary to myeloproliferative etc
decreased excretion: diuretics, lead poisoning, CKD
14
Q
name of acute vs chronic gout
A
acute = podagra chronic = tophaceous
15
Q
what does -ve birefringent mean?
A
blue when perpendicular to axis of red compensator
16
Q
how does colchicine work?
A
inhibit manufacture of tubulin
= reduced motility of neutrophils
17
Q
MoA of probencid
A
uricosuric
increases FEUA
18
Q
who should not be given allopurinol?
A
patient on azathioprine
19
Q
in what patients does pseudogout occur in?
A
patients with osteoarthritis
20
Q
what is the biggest lipoprotein?
A
chylomicrons
21
Q
what do CM and VLDLs contain?
A
high in TGs
22
Q
what are the features of LDLs
A
smaller than VLDLs
main carrier of cholesterol
23
Q
describe how cholesterol gets absorbed, what transporters?
A
- cholesterol solubilised in mixed micelles
- transported across intestinal epithelium by NPC1L1
- ABC G5 and ABC G8 transporters = transport cholesterol back into lumens of intestine
balance between these determines net absorbed
24
Q
what happens when cholesterol arrives at the liver?
A
it downregulates HMG-CoA reductase
25
what does HMG-CoA reductase do?
produce cholesterol from acetate and mevalonic acid
26
what are the 2 fates of cholesterol in the liver?
1. hydroxylation into bile acids: by 7 alpha hydroxylase
| 2. esterification into cholesterol esters: by ACAT
27
how do VLDLs form? help of what transporter?
cholesterol + TGs + apoB packaged into VLDL
| with help of MTP transfer protein
28
what is the main precursor for LDL?
VLDL
29
what does HDL do? what transporter?
pick up excess cholesterol from periphery
| ABC A1: packages free cholesterol from periphery into HDLs
30
what does CETP do?
cholesterol ester transfer protein
mediates movement of:
- cholesterol from HDL to VLDL
- TG from VLDL to HDL
31
what is the transport of TGs?
1. fatty foods to fatty acids
2. fatty acids synthesised into TGs
3. CM broken down into free fatty acids by lipoprotein lipase in capillaries
4. free fatty acids taken up by liver/adipose tissue
32
what happens to these free fatty acids when in the liver?
FFAs --> TGs --> packaged into VLDL
33
what mutations cause familial hypercholesterolaemia (II)?
dominant mutation of:
| LDLR, ApoB, PCSK9
34
what causes familial hyperalphalipoprotieinaemia?
increase HDL due to deficiency of CETP
| protective
35
what causes phytosterolaemia?
mutations in ABC G5 and ABC G8
| these normally prevent absorption of steroids
36
what does PCSK9 do?
promotes degradation of LDL receptor
| less LDL removed
37
cause of primary hypertriglyceridaemia type 1
deficiency of lipoprotein lipase (normally degrades CM)
| deficiency of ApoCII
38
cause of primary hypertriglyceridaemia type 4
increase synthesis of TGs
39
cause of primary hypertriglyceridaemia type 5
deficiency of ApoAV
40
how does nephrotic syndrome effect fats?
loss of protein in urine
decrease serum albumin
increase LDL synthesis
41
A-lipoproteinaemia
deficiency of MTP
| low levels of cholesterol
42
Tangier disease
HDL deficiency
| ABC A1 mutation
43
how do fibrates work?
lower TGs
44
MoA of ezetimide
cholesterol absorption blocker
| blocks NPC1L1
45
MoA of colestyramine
reduced bile acid absorption
46
Roux-en-Y
distal part of jejunum anastomosed to stomach
47
Bilopancreatic diversion
connection made from stomach to terminal ileum
48
calculating pH
pH = log 1/[H+]
49
how is bicarbonate calculated in lab?
[H+] = k x [CO2] / [HCO3-]
50
what acid base balance does hypokalaemia cause?
metabolic alkalosis
51
causes of metabolic acidosis
increase H production (lactic acidosis/ketoacidosis)
increase H excretion (renal failure, RTA)
loss of bicarbonate (fitula)
52
enzyme implicated in Gilberts
UDP glucuronyl transferase
53
B1 deficiency causes
Beri Beri
54
B3 deficiency
Niacin
| Pellagra
55
what is PKU? How does it present?
phenylalanine hydroxylase deficiency
phenylananine --> tyrosine
present: low IQ
56
sensitivity
TP/ total number with disease
57
specificity
TN/ total number without disease
58
PPV
TP/ total number with positive test result
59
what is included in the Guthrie test?
```
congenital hypothyroidism
SCD
CF
MCAD
PKU
```
60
what is MCAD?
fatty acid oxidation disorder
| can't produce acetyl-CoA from fatty acids
61
tx of MCAD
make sure child doesn't get hypoglycaemia
62
what is homocysteinuria?
failure of remethylation of homocysteine
63
how does it present?
lens dislocation
mental retardation
VTE
64
what is the CF screening test?
immune reactive trypsin
65
what is urea cycle?
takes ammonia, produces urea
7 enzymes in the pathway (disorders in all)
= HIGH AMMONIA
66
investigation findings in urea cycle disorder
increase glutamine
increase ammonia
urine orotic acid
67
treatment of urea cycle disorder
remove ammonia, low protein diet
68
what are the key features of urea cycle disorders?
- vomiting without diarrhoea
- respiratory alkalosis
- hyperammonia
- neuroencephalopathy
- avoidance/change in diet
69
features of organic acidurias
- hyperammonaemia
- metabolic acidosis
- high anion gap
70
what is the defect in organic acidurias?
defects in complex metabolism of branched chain amino acids
71
presentation of organic acidurias
unusual odour
lethargy
feeding problems
72
how do mitochondrial fatty acid and beta oxidation diseases present?
hypoketotic hypoglycaemia
73
what are the carbohydrate disorders?
disorders of breaking down carbs
1. galactosaemia
2. glycogen storage disease 1 (Von Gierke disease)
74
what is the deficiency in Galactosaemia?
Gal-1-PUT deficiency
75
presentation of Galactosaemia
```
D+V
conjugated hyperbilrubinaemia
sepsis
hypoglycaemia
bilateral cataracts
```
76
what is the issue in glycogen storage disorders?
lack a phosphotase
increase glycogen in muscle, liver
= hypoglycaemia
77
features and examples of mitochondrial disorders
heterplasy
multi-system, especially high energy organs
e.g. Barth, MELAS, Kearns-Sayre
78
what are the differences in the neonatal kidneys?
- low GFR for SA
- short PT = decreased resorptive capability
- decrease resorption of bicarb
- decrease concentrating ability
- DT unresponsive to aldosterone = Na loss
79
reasons for neonatal hyperbilirubinaemia
- high levels of bilirubin synthesis
- decrease rate of transport in liver
- enhanced enterohepatic circulation
80
causes of prolonged neonatal jaundice
- sepsis/hepatitis
- hypothyroidism
- breast milk jaundice
81
causes of conjugated hyperbilirunaemia
- biliary atresia
- ascending cholangitis in TPN
- metabolic disease (e.g. galactosaemia)
82
genetic causes of rickets
- pseudo-Vit D def I (defective renal hydroxylation)
- pseudo-Vit D II (receptor defect)
- familial hypophosphaetamemia (dec reabsorption)
83
what makes haem?
made in all cells by ALA synthase
84
what molecule causes neurovisceral symptoms?
5-ALA
| neurotoxic
85
what causes the skin lesions in pophyria?
due to accumulation of porphyrinogens in skin
| = oxidised by UV light in circulation
86
what is the most common porphyria?
porphyria cutanea tarda
87
what is the most common porphyria in children?
erythopoietic protoporphyria
88
what does ALA synthase deficiency lead to?
sideroblastic anaemia
89
what does PBG synthase (aka ALA dehydratase) deficiency leave to?
acute porphyria
| = increase ALA = neuro symptoms, abdo pain
90
what enzyme deficiency causes AIP?
HMB synthase
| = increase in PBG and ALA
91
symptoms in AIP
neurovisceral attacks, no skin symptoms
92
precipitating factors in AIA
ALA synthase inducers (e.g. steroids, alcohol), stress, decrease calorie intake
93
treatment of AIP
- avoid attacks
- IV carbohydrate (inhibits ALA synthase)
- IV haem arginate
94
what are the 2 acute porphyrias with skin manifestations?
1. hereditray coproporphyria
| 2. variegate prophyria
95
deficiency in hereditary coproporphyria
coproporphyrinogen oxidase
96
deficiency in variegate porphyria
protoporphyrinogen oxidase
97
features of HC and VP
AD
neuro attack
skin lesions
98
how to differentiate all of the different acute prophyrias
check urine and faces for porphyrins
high = HCP and VP
not high = AIP
99
non acute porphyrias?
- congenital erythopoetic porphyria
- porphyria cutanea tarda
- erythropoietic protoporphyria
100
enzyme deficiency in congenital erythropoietic prophyrra
uroporphyinogen III synthase
101
deficiency in prophyria cutanea tarda
uroporphyrinogen decarboxylase
102
enzyme deficiency in erythopoietic protoporphyria
ferrocheletase
103
what are EPP and CEP associated with?
myelodysplastic syndrome
104
what does percholate block?
blocks uptake of iodine to thyroid cells
105
what should you do if starting thyroid meds?
ECG
| increase myocardial contractility and may be at risk of ischaemia
106
what does excessive thyroxine?
osteopaenia and AF
107
what are the levels in subclinical hypothyroidism?
T4 level is normal
| TSH is high
108
what is subclinical hypothyroism associated with?
hypercholesterolaemia
109
what is the MoA of thionamides?
prevent conversion of iodide to iodine by TPO
110
what are the roles of PTH?
1. liberation of Ca from bone and increased resorption in kidneys
2. stimulates 1 alpha hydroxylase = production of calcitriol
3. stimulates renal phosphate excretion
111
progress of cholecalciferol
cholecalciferol to 25-OH D3 (stored/active form)
| 25-OH D3 to 1,25(OH)2D3 (kidney)
112
what is ALP a by product of?
osteoblast activity
113
what is Z-score?
age matched control
114
what does ADH act on?
acts on V2 receptors in collecting fuct
115
what is the most reliable clinical sign of hypovolaemia?
low urinary Na (<20)
116
how does cirrhosis cause hyponatraemia?
release of various vasodilation = dec perfusion
117
osmolality in SIADH
dec plasma osmolality
| inc urine osmolality
118
SIADH treatment
Demecyclyine
| Tolvaptan
119
treatment of hypernatraemia
use dextrose
| replace fluid without excess salt
120
what does angiotensin II stimulate?
adrenals to produce aldosterone
121
what does aldosterone do?
Na resorption
K excretion
(causes reduced degradation of Na channel)
122
what are the causes of hyperkalaemia?
- dec GFR
- inc renin activity (T4 RTA, NSAIDs)
- ARBs
- aldosterone antagonist
- K release from cells
- Addisons
123
what causes a hypokalaemia?
- GI/ renal loss
- redistribution
- Rare: RTA 1/2, hypomagnesaemia
124
what do Loop diuretics/ Bartter syndrome?
block triple transporter in ascending LOH
| = more Na delivery to distal nephron = K+ loss
125
what do Thiazide/Gitelman syndrome do?
mutation in Na/Cl channel
| = more Na delivery + K loss
126
what causes a high aldosterone:renin ratio?
primary hyperaldosteronism
| = high aldosterone will suppress renin
127
what is the normal anion gap?
14-18
128
what is Shmidt's syndrome?
primary hypothyroidism and addisons
129
what is Phaeo associated with?
MEN2
VHL
Neurofibromatosis type 1
130
test to do in Cushing's
inferior petrosal sinus sampling
131
what improves survival in BP and diabetes?
aggressive management of BP and lipids improves survival = add thiazide
132
what is Evolocumab?
PCSK0 monoclonal Ab
133
what does a loss of function mutation in PCSK9 result in?
higher LDL receptor levels
= lower LDL cholesterol levels
so if inhibit PCSK9 = removal of LDL cholesterol from plasma
134
what did the UKPDS do?
T2DM
blood glucose control must be good from beginning
= legacy effect
135
what did the Accord show?
sudden aggressive control of blood glucose in people with poor control
= decreased complications, increased mortality
136
what is an example of a SGLT2 inhibitor?
empagliflozin
137
what is the MoA of SLGT2 inhibitors?
wee out glucose
| decrease blood glucose and decrease BP
138
what is an example of GLP1 analogues?
exanatide/ semiglutide
139
what is the MoA of GLP1 analogues?
causes increase insulin from pancreas, incretin effect
140
what is an example of DPP-4 inhibitor?
Sitagliptin
141
what do DPP-4 inhibitors do?
break down GLP-1
142
symptoms of hypoglycaemia
adrenergic (tremors, palpitations, sweating)
| neuroglycopaenic (confusion, coma)
143
what is the order of hormone change in hypoglycaemia?
1. suppression of insulin
2. release of glucagon
3. release of adrenaline
4. release of cortisol
144
example of sulphonylurea
Glipizide
145
MoA of sulphonylurea
increase insulin release by binding ATP-sensitive K+ channels
146
how do you calculate clearance?
clearance = (urinary concentration x volume)/ plasma concentration
147
what is the current eGFR recommended calculation?
CKD-EPI
148
what type of casts in ATN?
epithelial casts
149
CKD stages based on GFR levels
1. kidney damage, normal GFR (>90 ml/min)
2. 60-89 ml/min
3. 30-50 ml/min
4. 15-29 ml/min
5. ESRF <15 or dialysis
150
what causes adynamic bone disease?
excessive suppression of PTH
| = lower turnover and decreased osteoid
151
high dose dexamethasone result
complete failure to suppress dexamethasone = ectopic
| pituitary = can be suppressed by high dose dexa
152
what happens at high levels of cortisol (e.g. ectopic ACTH)?
cortisol can bind to aldosterone receptors
153
CPFT
insulin to induce hypoglycaemia
TRH
LHRH
154
cause of ALP > x5 ULN
Paget's
osteomalacia
cholestasis
cirrhosis
155
cause of ALP < x5 ULN
fractures
osteomyelitis
infiltrative disease
hepatitis
156
statin enzyme
CYP3A4
157
Vit A (retinol)
Deficiency
Excess
Test
Def: colour blindess
Excess: exfoliation hepatitis
test: serum
158
Vit D (Cholecalciferol)
Def: osteomalacia
Excess: hypercalcaemia
Test: serum
159
```
Vit E (tocopherol)
deficiency
test
```
Def: anaemia/ neuropathy/ malignancy/ IHD
test: serum
160
B1 (thiamin)
Def
Test
Def: Beri Beri neuropathy, Wernicke
Test: RBC transketolase
161
B2 (Riboflavin)
Deficiency
Test
Def: glossitis
Test: RBC gluthione reductase
162
B6 (Riboflavin)
Def
Excess
Test
Def: dermatitis/ anaemia
Excess: neuropathy
Test: RBC AST activation
163
Niacin deficiency
pellagara
164
types of Beri Beri
```
Wet = CVD
Dry = Neuro
```
165
what is PYY?
satiety hormone
| increases after meal
166
what is Leptin?
anti-hunger hormone
167
what waist circumference major risk?
men: >102
women: >88
168
features of metabolic syndrome
```
fasting glucose > 6.0
HDL: men <1.0, women <1.3
waist circumference: men >102, women >88
HTN: BP >135/80
microalbumin, insulin resistance
```
169
AST: ALT >2
alcoholic liver disease
170
cause of isolated ALT
fatty liver disease
171
what are the liver dye tests? use?
Indocyanine green/ Bromsulphalen
| measures excretory capacity of liver, measures hepatic blood flow
172
enzymes that increase following MI
troponins
CK (MB)
AST (3-14 days)
LDH
173
scan for primary neuroendocrine tumours
Gallium 68 dotate scan
174
parathyroid scan
sesta MIBI
175
phae scan
MIBG
176
gram -ve intracellular diplocci
Neisseria
177
Gram +ve cocci
strep viridans
178
where does strep viridans affect?
on damaged valves
| aortic and mitral valves
179
what kind of deafness does Paget disease cause?
conductive
