Chempathology Flashcards
1
Q
What are the management options for acute hypoglycaemia
A
Alter & orientated - carbs -Rapid= juice/ sweets -long-acting - sandwich Drowsy/ confused -Buccal glucose, hypo stop/ glucogel. Consider IV access Unconscious/ unsafe swallow -IV 50ml, 50% glucose mini-jet or 100ml 20%
IM glucagon Img ( deteriorating, refractory, insulin-induced, difficult IV
All should be monitored
2
Q
What glucose range is hypoglycaemia
A
<3.5 mmol
Worried <3mmol/L On ward <4mmol/L Neonates <2.5mmol/L (normal is 4-6mmol, can drop lower,3-3.5 following exercise or excessive carbohydrates) \+ symptoms
3
Q
What are the symptoms of hypoglycaemia
A
Early Adrenergic: tremors, palpitation, sweating, hunger.
(may not occur in insulin-treated diabetics who are chronically hypo)
Neuroglycopenic: confusion, seizures, coma, death
Should resolve with glucose
4
Q
What is the order of physiological changes during hypoglycaemia
A
- insulin suppression
- # Increase glucagonv peripheral glucose uptake
^glycogenolysis
^gluconeogenesis
^lipolysis -> ^free fatty acids (beta-ox ->^ ATP and ketones) - Adrenaline (=slight insulin resistance)
- ACTH, cortisol and growth hormone.
5
Q
What are the investigation confirms hypoglycaemia
A
Confirm hypoglycaemia
- bm (easy in diabetes, but is inaccurate due to poor precision in normal adults)
- lab (grey top -fluride oxalate- 2mls blood -gold standard)
6
Q
What are the causes of hypoglycaemia (without diabetes) (6)
A
Fasting vs reactive
Critical illness, organ failure- liver and renal (no gluconeogenesis), hyperinsulinism, post gastric bypass, drugs, extreme weight loss - eg anorexia, factious
7
Q
What are the causes of hypoglycaemia in diabetes (5)
A
Hypo unawareness (can be caused by autonomic neuropathy)
Excess insulin or sulphonylureas
Excess EthoH (decreased awareness and ^ glucose)
Strenuous exercise
coexisting AI (additions due to lack of steroids)
8
Q
What medications can cause hypoglycaemia in diabetes
4 diabetes) (3 other
A
That can cause hypos:
Sulphonylureas and insulin- rapid and long actin.
-Meglitinides, GLP-1
-beta-blockers, salicylate, alcohol
9
Q
What investigations should be done for hypoglycaemia (non-diabetes)
A
Must be done during the hypo
-Full Hx and Ex
-Need to consider IV access and treatment vs tests
- Bloods: Glucose, Insulin, C-peptide, drug screen , Auto-antibodies, cortisol, GH
FFA, ketones
specialist IGFBP, IGF-2, carnities
10
Q
Why is measuring c-peptide useful
A
As it is the cleavage product of pro-insulin, it is secreted in equimolar amounts to insulin but has a long T1/2 (30 mins) compared to insulin (minutes)
It can help to determine if insulin is exogenous or endogenous. (c-peptide would be low if exogenous insulin)
11
Q
How can anorexia cause hypoglycaemia
A
Chronically poor dietary intake can cause depletion of liver glycogen stores
+ acute lack of glucose intake
12
Q
What can cause hyperinsulinaemic hypoglycaemia?
A
Fasting, critical illness, Anorexia, strenuous exercise, endocrine deficiencies (eg v hypo pit or hypoadrenalism)
Failure- liver, anorexia Nervosa
13
Q
What are the causes of neonatal hypoglycaemia
A
appropriate (and will improve with feeding)
-Prem, IUGR, small for gestational age, inadequate glycogen and fat stored.
pathological
-inborn errors of metabolism
14
Q
What are the investigation finding in inborn errors (give examples) of metabolism (neonatal hypoglycaemia)
A
^FFA, no ketone bodies
-Fatty acid oxidation disorder - no ketone production
- Glycogen storage disease T1- gluconeogenic disorder
-Medium-chain acyl-CoA dehydrogenase (MCAD)
Carnitine disorders
15
Q
What metabolic disorders are screened for on the Guthrie blood spot test ( and their pathology)? (9)
A
Phenylketonuria (phenylalanine hydroxylase v- check levels)
SCD,
MCAD, maple syrup urine disease (MSUD), isovaleric acidaemia, homocystenuria, glutamic acid type 1,
SCID
CF (CFTR gene mutation, immune reactive trypsin+), Congenital hypothyroidism (dys/agenesis of the thyroid gland -TSHv)
16
Q
Define specificity and sensitivity, PPV / NPV
A
Specificity= Total Negative (False positive+Total negative)
-that someone without the disease will correctly test negative
Sensitivity= Total positive/ (Total positive+ False negative)
- the probability that someone with the disease will test positive
Positive predictive value= Total positive/ (Total positive+False positive)
Negative predictive value = Total negative/ (Total negative +False negative)
17
Q
What are the different types of metabolic conditions
A
Accumulation of toxins Poor energy stores Large molecule synthesis errors in large molecule metabolism Mitochondrial
18
Q
What metabolic conditions are classified as the accumulation of toxins (3-groups)
A
Organic acidaemia eg propionic (Ketosis, metabolic acidosis, acidaemia
Urea cycle disorders - eg ornithine transcarbamylase v
Amnioacidopathies- PKU, maple syrup urine disease
19
Q
Which metabolic disorders are caused by defects in large molecule metabolism?
A
Lysosomal disorder eg Tay Sachs disease
20
Q
What are the general symptoms of hypocalcaemia
A
bone disease, muscle and nerve hyperexcitability
21
Q
What are the symptoms of hypercalcaemia
A
Bones- boney pain, Stones- renal caulculi, Groans- constipations and Moans - confusion >3mmol/l, seizures coma, Polyuria and poldipsia, osmotic diuretic
22
Q
What is the function of PTH
A
PTH - increases serum calcium (neutral effect on Pi)
Bones -^ Ca and Pi release - ^osteoblast activation -> ^ proliferation, ^RANK L expression, v OGT expression (this prevents interference with RANK L) -> ^ osteoclast activity
^ Calcitonin - ^ bones and ^ GI
Direct ^ Ca absorption in GI, (indirect via calcitonin for Pi
Kidneys - ^ 1a hydroxylase > ^ active vitamin D, ^ Ca reabsorption, ^ excretion of Pi
23
Q
How is active vitamin D formed
A
Cholecalciferol
Ergocalciferol - dietary
transformed in the liver to 25,OH D3
1 alph hydroxylase in kidneys -> 1,25 diOH D3
24
Q
What is the role of vitamin D
A
^ GI absorption of ca and Pi, affects cell proliferation and immunity
25
Which bone disease have
a. normal calcium
b. low calcium
c. high calcium
a. Paget's - just abnormal structure, Osteoporosis - everything is normal except BMD
b. v Vit D - osteomalacia, ricket's, renal osetodystrophy -v reasorption and v vit D, pseudohyperparathyroidism, hypoparathyroidism
c. 1 ^PTH, cancer, thiazides, sarcoidosis
26
Which bone disorders result in an elevated ALP?
Paget's, Vit D deficiency
| ^/- Primary and secondary PTH++
27
What is the normal range of sodium?
135-145mmol/L
28
What are some causes of hyponatraemia (volume split)
Hypovolaemic - Fluid loss, GI- D&V, renal- salt loosing nephropahty
Euvolaemic- Hypothyroidism, adrenal failure, SIADH
Hypervolaemic - HF, cirrhosis, renal failure
29
What are some causes of SIADH
Respiratory - infection- pneumonia, aspergillosis, abscess, TB
Malignancy- lung small cell or mesothelioma, Gi- stomach, duodenum, pancrease.
CNS- SOC - cancer, bleed, stoke, GBS, MS,
Drug induced- SSRIs, TCA, antipsychotics, MDMA, desmo/vassopressin, oxytocin, opiates
Other- any nause and vomiting, pain, stress, hereditary
30
What are the investigations for hyponatraemia?
| Volume split
Assess fluid status - clinical exam and full obs
Hypovolaemic- FBCs, CRP, U&Es- eGFR
Euvolaemic - TFT, short synthactin test, urine and plasma osmolality
Hypervolaemic- ECG/echo, LFTs, U&Es and eGFR
31
What are the investigations for hypernatraemia
bloods - glucose (rule out DM), K+, Ca+ (rule out nephrosis), plasma and urine osmolality
32
What is the management of hyponatraemia (split by fluid)
Hypovolemic- normal saline
Euvolaemic - fluid restriction - if very deficient consult a specialist for initiating 3% saline - do not increase by >8-10% in first 24hrs, <10 after that.
Hypervolaemic - fluid restriction <750ml/ day including abx drip
Always treat underlying cause
33
What is the management of hypernatraemia?
5% dextrose
| If hypovolaemic 0.9% normal saline followed by 5% dextrose.
34
What are the diagnostic criteria for SIADH
Euvolaemic hyponatraemia
with normal TFTs and adrenal function
low serum and increased >100 urine osmolality
35
What is the normal range of plasma potassium?
3.5-4.5mmol/L
36
```
What is the effect of
a. aldosterone
b. insulin
c. beta-agonists
d. loop diuretics
e. spironalcatone
on plasma potassium
```
a. v (via increased excretion of K+ in CD down an electrochemical gradient to compensate for water and Na+ reabsorption.
b. v (Increased uptake into cells)
c. v (also ^ uptake to cells)
d. v (triple transporter inhibition> v K+ reabsorption)
e. ^ - anti-aldosterone
37
What are the causes of hyperkalaemia?
Renal dysfunction - diabetic nephropathy, NSAIDs
v Aldosterone: Addison disease and malignancy
^ release from cells: Acidosis, Rhabdomyolysis
Drug-induced - ACEi, ARBs, spironolactone
ps - consider a haemolysed sample
38
What is the treatment of hyperkalemia?
```
>6.5 and or ECG changes
10ml 10% calcium glucontae
50ml 50% dextrose + 10 U insulin
Nebulised salbutamol
<6.5 and no ECG changes - treat cause
```
39
What are the causes of hypokalaemia?
GI loss - D and V
Renal - ^ aldosterone/ ecess cortisol
^ Na+ reaching DCT - eg loop diuretics, thiazides (nieche batter syndrome, Gitleman, v magnesium, renal tubular acidosis T1 and 2)
osmotic diuresis - eg DM
40
What is the treatment of hypokalaemia
3-3.5 oral KCL TDS 48hrs
| < 3 IV KCL max 10mmol/L/Hr ( peripheral vein irritation)
41
What are the clinical finding of hyperkaelmia? (Ecg)
ECG- peaked t waves, flattened p waves, prolonger PR interval, bradycardia
42
What are the clinical signs and symptoms of hypokalaemia
Cardiac arrhythmias, muscle weakness, poluria and polydipsia
43
What are the buffering methods for pH?
^ Renal excretion of H+ > ^ regeneration of bicarb -. mop up H+
^ respiration rate to blow off CO2 > shifts equation to replace CO2 + v CO2
44
What are the VBG finding of
a metabolic acidosis
b. with compensation
a. acidotic <7.35, normal PCO2(4.7-6.0), normal PO2 (10-13), vHCO3 (<22) (if normal consider other acids eg lactate, ketones)
b. v or normal pH, vPCO2, normal PO2, vHCO3
45
What are the VBG findings of
a. respiratory acidosis
b. with compensation
a. ph <7.35, pCO2 >4.7, pO2 - variable - depending if on oxygen and severity, HCO3 normal 22-30
46
What are the causes of respiratory acidosis?
v lung perfusion - PE, RHF
V/Q mismatch
v gas exchange - emphysema
47
What are the causes of metabolic acidosis?
^anion gap MUDPILES
Methanol, Uraemia DKA Propylene glycol Iron tablets Lactic acid Ethelene glycol Salicylates
normal anion gap 6-12 HARDASS
Hyperpigmentations Addison's Renal tubular necrosis Diahorrea Acetocolamide Spironolactone (^K+) Saline
48
What are the causes and findings for metabolic alkalosis?
pH >7.46, pCO2 normal( 4.7-6.0), pO2 (10-13) normal, HCO3 >22
Compensated - pH v/-, PCO2^, pO2 -, HCO3 >22
Causes: Bicarb intake - antacids, H+ loss- vomiting, Hypokaleamia
49
What are the causes and findings of respiratory alkalosis?
pH >7.46, PCO2 <4.5, PO2, HCO3 -
compensated pH ^/-, PCO2 <4.5, HCO3v
causes: hyperventilation - panic attack, drugs, artificial ventilation
50
Why is respiratory compensation for metabolic alkolosis limited?
^PCO2 will stimulate the respiratory drive to increase resp rate.
51
What is the equation for osmolality
=*2(Na+K+)+ urea + glucose
52
How is the anion gap calculated?
= Na+ K+ - (Cl- and HCO3-)
53
What do the liver function tests look at?
AST- liver, (muscle kidney, brain, pancreas)
ALT- liver (muscle, kidney brain pancreas)
ALP - Gallbladder (also bone) (SI, kidney, WBC, placenta)
GGT- gallbladder, chronic alcohol intake (kidney, pancreas, spleen heart, brain, seminial vesicles, liver)
Bilirubin- pre- haemolysis, intra- liver function, post- obstruction
Albumin- chronic synthetic function (T1/2= 20 days)
PT- acute synthetic function
aFP- HCC, pregnancy, prostate cancer
54
What are the functions of the liver
intrametabolic- GNG, glycogenolysis, lipid met, FA synth
protein synthesis
xenobiotics- p450, redox, conjugation, excretion
Hormone met
Bile synthesis
Reticulo-endotheliasl- epo and kuffer cells
55
When is it important to look at AST and ALT together
AST:ALT ratio >2 indicates alcoholic hepatitis.
| >1 but no alcohol history indicated severe cirrhosis-> need further imaging
56
How should you interpret a raised bilirubin?
If AST and ALT are raised - intraheptaic causes
If GGT or ALP are raise- cholestatic - USS - dilated - obstruction, undilated- drugs, PSC, PBC
neither - blood film for haemolysis or gilbert
57
What tests are on a liver screen (aka what to do after abnormal lfts)
```
HBV and HCV
Fasting lipids and glucose
Ferritin and iron studies
coeliac
haemosiderin
Ceruloplasmin <50 Wilson's->urinary copper
Auto antibodies- ASMA, AMA,ANCA
ALpha-1antitrypsin -> phenoptype
```
```
Imaging
USS
CT
MRCP
Endoscopic US
```
58
Which zone of the liver is most susceptible to hypoxia and why
Zone 3 as it has the highest metabolic rate and is furtherest form the afferent blood supply
59
What are the histology finding of acute hepatitis?
Fatty depositis, megamitochondria
-Mallory hyaline (stains pink) lines -> ballooning which is irreversible damage.
Cirrhosis forms small nodules
60
What is the treatment of alcoholic hepatitis?
Stop drinking
Parinex
Steroids - contentious
61
What is the treatment of portal hypertension?`
Beta blockers
Sclerotherapy for anastomes
Terlipressin for active bleeding
62
What is the normal histology of the liver?
portal triad contains portal vein, hepatic artery and bile ducts. Hepatocytes are organised in trabeculae with central sinusoids that surround a central vein
63
What anastomes get engorged in portal HTN
```
Oesophageal
Umbilical
Anal
Retroperitoneal
bare area of liver
Patent ductus venosus - rare
```
64
What are the definitive features of liver failure
Failed synthetic function - eg ^INR/PT, v albumin
^ amnion -. encephalopy
Failed clearance of bilirubin
65
Which hormones are released from the pituitary?
Anterior - ACTH, GH, LH and FSH, TSH prolactin
| Posterior - vasopressin and oxytocin
66
What is the cause of SHeehan's syndrome?
MOH - leads to ischamia of the pituitary gland - which increases in pregnancy.
Characterised by failure to breast feed, amenhorrea and tiredness
67
What are the indications for a pituitary function test
Gynaecomastia and amenhorea
68
WHat are the causes of a raised prolactin?
>6000 = prolactinoma
Disconnected hyprolactinaemia =non-functioning pituitary adenoma - causes compression of the stalk > v dopamin > ^ prolactin
Pregnancy
Hypothyroidism (^TRH > ^prolactin
69
How is the triple pituitary stress test done?
Fatsed overnight
Given TRH, LHRH and insulin
- measure glucose, TSH, GH, Lh and FSH and basal thyroxine every 30 mins.
Can be dangerous so need ECG and IV access prior- to give dex
70
What are the investigations for acromegaly?
OGTT- should suppress GH
| IGF-1 and exercise tests
71
What are the investigations for suspected GH deficiency in children
Random GH
Exercise tolerance test
Insulin stress test - not first line as dangerous
72
What is the order of importance for pituitary hormone replacement?
Cortisol (hydrocortisone)> Thyroxine>oestrogen> growth hormone
73
Describe the synthesis of T3 and T4
TRH->TSH-> thyroid.
Uptake of iodide via -Na+/I- symporter- bl mem.
I- -> folliclular space via CL-/I- antiporter on apical mem
TPO oxidises I- ->I
Iodinisation of thyroglublin -> MIT or DIT
MIT + DIT = T3
DIT x2= T4
Stores in lysosome
Released directly into blood stream
74
What are the signs and symptoms of Hypothyroidism?
Bradycardia, weight gain, poor appetite, cold intolerance, constipation, low mood, oligo/amenorrhea -> infertility, fatigue, laboured breathing, hyponatraemia, normocytic anaemia, myoedmea, goitre
75
What are the causes of hypothyroidism
Hashimoto's, post-viral thyroiditis, congenital/ acquired, thyroidectomy/ radio, drugs- amiodarone and lithium
Dysgenesis/agenesis
Pituitary dysfunction
Thyroid hormone resistance
76
WHat are the investigations for hypothyroidism
TSH, T3, T4, AI screen, ECG
77
What are the signs and symptoms of hyperthyroidism?
Tachycardia, sob, diarrhoea, oligomenorrhea, palpitations, AF, sweating, anxiety, increased appetite, ^ energy , osteopenia
(Grave's- exopthalmos, pretibial myxoedma goitre, thyroid acropatchy (fat fingers)
78
What are the causes of hyperthyroidism?
High uptake: Grave's disease, toxic nodular, single toxic nodule
Low uptake: thyroid cancer, silent thyroiditis- immune and amiodarone, TSHoma, viral thyroiditis, factitious, trophoblastic stumour, struma ovarii
79
What are the investigations for Hyperthyroidism?
TSH, T3, technetium uptake scan, AI screen, dexa
80
How is thyroxine affected by pregnancy?
Beta HCG stimulates T4 synthesis-> v TSH.
Also ^ TBG due to ^oestrogen= maintained fT4
3rd trimester -> HCG v-> ^TSH
81
What thyroid dysfunction is screen for in neonates?
Congenital hypothoroidism on the Guthrie test
48-72hrs
(earlier= maternal, >5 days later = too late to prevent neurodisability)
82
What is sick euthyroid?
Severe (non-thyroid) illness eg sepsis -> vfT3 and action, compensatory ^TSH and normal T4
- does not have clinical signs of hypothyroidism and does not respond to levo
83
What are the different types of thyroid cancer?
Medullary- sporadic or MEN2- markers= calcitonin and CEA, Papillary
Treatment is surgical resection or thiamides (cabergoline)- TG = marker of relapse
84
What is functionality of measuring enzymes?
Localised damage - leaky membrane -> release of cytosolic enzymes
Necrosis -> intra-organelle enzymes
Local- cell damage- synthesis
Response to treatment
Marker for substrate- eg glucose oxidase for glucose
85
What causes raised ALP and how can you differentiate?
>x5 - Paget's disease, osteomalacia, 1 and 2 ^PTH, Cirrhosis, cholestasis
86
Describe the biomarker tests for myocarial infarction?
Myoglobin (non specific)
troponin- being to rais from hrs 4-6, peak at 12-24 and slowly decline over 3-10 days
MB- CK- rapid increase and decrease
87
What can cause a raised amylase?
>x10 Pancreatitis- (check lipase as more specific)
any acute abdomen
Salivary form- mumps and parotitis
88
What are the signs and symptoms of Addison's
Significantly worse during acute stress - eg illness, surgery
Weak, dizzy, fatigue, anorexia, muscle or joint pain, D&V, back pain, abdominal pain, hypotension, hyperpigmentation
89
What are the features and treatment of a phaeo
Acute hypertension, aggression
| Treat with alpha, beta, surgical removal
90
Which hormones are produced in the adrenal glands
Adrenal medulla- catecholamines Noradrenaline and adrenaline
Cortex
Zona glomerulosa- mineralcorticoids- aldosterone
Zona fasiculata - glucocorticoids cortisol
Zona reticularis- androgens
91
What is the test for addison's disease?
Short synthactin test - measure cortisol, give synthetic ACTH measure cortisol at 30 and 60 mins
92
What is the test for Conn's
Aldosterone and renin levels and CT
93
What is the tests for Cushing's
9am and midnight cortisol
Dexamethasone suppression test
pituitary sampling
MRI >5mm
94
What is the function of cortisol?
```
Opposite effect of insulin
^glycogenolysis
^lipolysis
^aminoacid breakdown
^osteoclast activity
^BP and HR
```
95
What are the requirements for a metobolite clearance = GFR
Freely filtered
not protein bound
not resorbed or excreted by tubular cells
96
What are the clinical markers of GFR
99Tc DTPA
51 Cr EDTA
creatinine
cystatin C
97
Why is creatinine not an accurate GFR
Proportional to muscle mass and injury
v with age
affected by ethnicity
Also variable renal excretion 30-60%
98
What are the different imaging types for kidneys
Renal USS - stones with hydronephrosis, AKI- kidney size
CTKUB - first line for stones
Histology
IV urogram - old
99
What is the definition of AKI?
Rapid declined in kidney function within hours resulting in an inability to maintain homeostasis in electrolytes, fluids or acid-base
100
What are the different types and aetiologies of AKI
pre renal - systemic v blood supple- hypovolemia, hypotension, 3rd spacing, renal specific (RAS), Drugs - ACEi, NSAIDs, calcineurin inhibitors, diuretics
Intra renal - heterogenous
Post renal - obstructive, renal, ureteric, prostatic (BPH, prostatitis and C), extrinsic- catheter > urinary retention
101
What are the classes of AKI
Class 1 Serial serum creatinine >26umol 1.5-1.9x normal
Class 2 SSc 2-2.9x normal
Class 3 SSc 3+x normal or 354umol/L
102
What are the consequences of CKD
Anamia of chronic disease- v EPO
CVD - vascular calficiation and uraemic cardiomyopathy
Uraemia
Hyperkalaemia- worsened by ACEi and spironalactone
Renal acidosis - v H+ excretion
103
What are the different types of renal bone disease
Osteitis fibrosa- ^ osteclast activity - replaced with fibrosis
Osteomalacia- v Vit D
Adynamic bone disease- vpth
Mixed osteodystrophy -^ 2nd and 3rd ^pth
104
What is the treatment of chronic kidney disease
Haemodialysis
Peritoneal dialysis
Transplant
Optimise HTN, lipids, DM
105
What are the causes of CKD (9)
```
DM - most common
HTN
ATN
Atherosclerosis > RAS
Drugs
Infective/ obstructive - bph
Poly cystic kidneys
Chronic glomerulonephrtisi
```
106
What is the difference between AKI and ATN
AKI is reversible damage that once renal blood flow is correct resolves v GFR
ATN is prolonged ischaemia > damage to tubular cells> irreversible
107
What are the interstial causes of AKI
Intrarenal- vasculitis, direct tubular injury- drugs, sepsis contrast dye, toxins - endogenous - myoglobin
exogenous- aminoglycosides, amphotericin and aciclovir
Glomerulonephritis and vasculitis
Abnormal protein deposition- amyloid, MM related, lymphoma
108
What are the criteria required of a screening program?
```
Important health issue
Ability to be diagnosed
Can be treated
Test suitable and acceptable to public
Scientific understanding of disease progression
Latent/ early symptomatic stage
Economically balanced
Agreed population that require treatment
```
109
Which disorders are screened for on the Guthrie?
Congenital hypothyroidism
severe combined immunodeficiency
CF
SCD
```
Phenylkenouria
Maple syrup urine disease
Homocysteine uria
Isovaleric acidaemia
Glutaric aciduria T1
MCAD
```
110
Define
a. sensitivity
b. specificity
c. positive predictive valvue
d. negative predicitive value
a. Ability to correctly identify positive cases = Ture+/total with disease
b. Ability to correctly exclude negatives= T-/ total without disease
c. PPV = True + / total +
d. NPV = true -/ total -
111
What are the general things diagnostic tests for metabolic disorder can look for?
Deficiency in enzyme >
Excess substrate
Deficiency in product
Abnormal metabolites (as when the substrate is in excess may be processed by alternative enzymes)
112
Describe the pathology and treatment of PKU
Phenylalanine hydroxylase deficiency> build-up of phenylalanine (essential amino acid) but CNS toxic > Ig <50
From <6 weeks limit intake but not completely
113
Describe the testing for CF
Blood spot -if IRT >99.5 centile (on 3 blood spots) - Test for 4 most common CFR mutations
2+ = CF
1 mutation > expand mutations to 28 most common
0 mutation > repeat IFT in 21-28 days
114
How does MCAD present and how can it be prevented?
Neonatal hypoglycaemia and - cot death
| Pt has an inability to under go beta-oxidation therefore treatment is regular feeding intervals
115
Describe the general presentation of a urea metabolic disorder and treatment?
```
Hyperammonaemia
Vomiting (no D), respiratory alkosis, encephalopathy, avoidance of protein, coma
```
labs= ^glutathione, ^/ absent AAs, coma if >300mmol/L ammonia
116
Describe the presentation of a hyperammoniamic organic metabolic acidosis
Non lactate metabolic acidosis with a high anion gap
Neonate : funny smelling urine, lethargy, Hypotonic trunk, hypertonic limbs
myoclonic jerks, coma
Older = recurrent ketoacidotic comas and cerebral abnormalities
117
Describe the presentation of reye syndrome
Induced by salicylates - eg asprin, antiemetics and valproate
Vomiting, lethargy, confusion, seizure, decerebration, respiratory arrest
118
What is the cause of organic hyperammonia acidosis?
Inability to process aminoacids with branched side chains eg leucine, isoleucine, valine
Inability to excrete these> ^ anion gap
119
When should you suspect a mitochondrial disorder and how would you confirm?
Multisystem involvement of highly metabolically activity - eg Brain, muscles, kidneys, liver, eyes, endocrine
Lactate^ even after fastine, ^CSF lactate and pyruvate, unexplained ^CK
Muscle biopsy= ragged red fibres
mitochondrial DNA analysis
120
WHat is the pathology of
a. lysosomal storage disorders
b. galactosaemia
c. glycogen storage disease T1 (von Gierke)
d. peroxisomal disorders
e. congenital disorders of glycosylation
a. Deficiency in different lyoszymes = heterogeneous presentations > intraorganelle accumulation >organomegaly
b. Inability to breakdown galactose (avoid all dairy) - Glactose-1-phophate uridyl transferase deficiency
c. Inability to dephosphyrlate G1p and G6P > ^glycogen stores > hypoglycaemia
d. Impaired metabolism of VLCFA and phospholipid synthesis
e. In ability to glycosylate proteins
121
What is the role of purines? (3)
Guanine, Adenosine (and intermediate inosine)
Genetic code
Secondary messenger cAMP, cGMP
Energy transfer ATP
122
Describe the catabolic pathway of purines? (including excretion)
Purines >Hypo xanthine > xathine > (xanthine oxidase)> urate (uritase is non functional in humans)
123
Why does gout typically affect the first MTP?
Gout affects the 1st MTP commonly because it is a distal cooler joint so more prone to precipitating out.
Urate circulates at a level close to the limit of solubility, and its solubility decreases at cooler temperatures and lower pHs.
124
What is the rate limiting step of denovo purine synthesis and the feedback it receives?
PAT
Negative feedback from adenosine and guanine
Positive feedback from PRPP (substrate and also part of the recycling pathway)
125
Explain the findings on joint effusion for gout and pseudogout?
Gout - negatively birefringent needles - appear yellow in the plain of the polariser and blue in the perpendicular plain as it has the ability to bend polarised light
Pseudogout - blocky crystals positively bifingent - blue in the plain and yellow perpendicular
126
What is the acute and chronic management of acute gout (podagra)?
Acute - NSAIDs (no if CKD), joint steroid, Colchine
| Chronic - ^water intake, reverse any contributing factors, allopurinol (do not give with azathioprine)
127
What is the pathology of lesch Nyhan syndrome
XR linked HPRT deficiency
| Inability to do salvage pathways > ^ PRPP > ^ PAT activity, vA and G > ^PAT activity
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What are the s&S of Lesch nyhan syndrome?
Well at birth, at 6 months > choriform movements, spasticity, self mutilation severe cognitive impairment, failure to reach milestons
