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1
Q

How is calcium divided up around the body

A

99% skeleton

1% serum

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2
Q

Forms of serum calcium

A

Free ‘ionised’ - 50%
Protein bound - 40% - to albumin
Complexed - 10% - citrate/phosphate

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3
Q

Calculating total calcium from ionised Ca.

Corrected calcium equation

Normal serum calcium

A 
Double ionised (If albumin is constant)
Total iron is what's given on lab tests so can use corrected ca formula to see if there is true increase/decrease in free ionised iron or if albumin is affecting

Serum calcium + 0.02(40-serum albumin)

2.2-2.6mmol/L

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4
Q

Which form of calcium in serum matters and why

A

Free ionised

Ca important in muscle depolarisation and nerve + muscle control

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5
Q

Effect of high albumin on free calcium

A

low (more bound)

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6
Q

Effect of low albumin on free calcium

A

high (less bound)

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7
Q

Hormones involved in calcium homeostasis

A 
PTH
Vit D (steroid hormone) - cholecalciferol (D3) is animal form
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8
Q

Summary of PTH function

A

Calcium absorption via 3 sources
Bone
Kidney (reabsorbs + Stimulates 1,25 (OH)2 vit D synthesis (1 alpha hydroxylation))
Gut (by vit D)

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9
Q

Process of Vit D synthesis

A

D3 synthesised in skin

Liver:
25-hydroxylation
(stored and measured form of vit D) - is inactive

Kidney - where activated
1 alpha hydroxylation (under PTH)

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10
Q

Roles of calcitriol

1,25 - dihydroxycholecalciferol

A

Intestinal Calcium absorption
Intestinal phosphate absorption
Bone formation

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11
Q

Roles of the skeleton (metabolic)

A

Metabolic role in calcium homeostasis

Main reservoir of calcium, phosphate and magnesium

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12
Q

Roles of the skeleton (orthopaedic)

A 
Structural framework
Strong
Lightweight
Mobile
Protect organs
Capable or orderly growth and remodelling
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13
Q

Metabolic bone disorders

A

1) Osteoporosis
2) Osteomalacia
3) Paget’s disease

Parathyroid bone disease
Renal osteodystrophy

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14
Q

Vit D deficiency clinical picture children

A 
Defective bone mineralisation - Rickets
Frontal bossing
Bowed legs (tibia)
Widened epiphyses ar wrists
Myopathy
Costochondral swellings
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15
Q

Vit D deficiency clinical picture adults

A 
Osteomalacia - demineralised bone
Bone and muscle pain
Increased fracture risk
Low Ca + Pi, raised ALP
Looser's zones
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16
Q

Osteomalacia in adults causes

A

Vit D deficiency:

  • Renal failure (1alpha hydroxylase lack)
  • Anticonvulsants (break down vit D)
  • Lack of sunlight
  • Chapatis (phytic acid) - questionable
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17
Q

What is osteoporosis

A

Normal bone but less - normal aging, normal biochem

Loss of bone density. Asymptomatic until first fracture

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18
Q

How is osteoporosis diagnosed

Score used
and meaning

A

DEXA scan - hip( femoral neck) + lumbar spine

T score >2.5 SD below normal

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19
Q

T score use
vs
Z score use

A

T score: sd from mean of healthy young pop
fracture risk

Z score: sd from mean of age-matched controls
accelerated bone loses in younger pts

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20
Q

Osteoporosis causes

A

Age, post menopausal: Primary reasons
Drugs (steroids), systemic diseases: Secondary reasons

Risk factors: Sedentary, Smoker, Shotter slim, childhood illness. Cushings, thyrotoxicosis, early menopause, hyperprolactinaemia,
Genetics, prolonged illness

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21
Q

Osteoporosis tx

A

Weight bearing ex
Stop smoking
Reduce alcohol

Drugs: Vit D/Ca
Bisphosponates (alendronate) - decrease bone resorption
Teriparatide
Strontium
Oestrogens - HRT
SERM - e.g. raloxifene
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22
Q

Bisphosphonates side effecct

A

GI

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23
Q

Hypocalcaemia signs

A

Neruomuscular excitability

  • Trousseau
  • Hyperreflexia
  • Chovstek’s sign
  • Convulsions
  • Prolonged Q-T
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24
Q

Aetiology of Hypocalcaemia dependent on

A

1) PTH driven - low PTH
- Surgery (thyroidectomy)
- Autoimmune hypoparathyroid
- DiGeorge syndrome
- Mg deficiency (needed for PTH production

2) Non-PTH driven
- Vit D deficiency
- CKD (1-alpha hydroxylation)
- PTH resistance (pseudohypoparathyroid)

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25
Biochem in secondary hyperparathyroidm
High PTH, low CA (lowest ever)
26
Response of PTH to hypocalcaemia if not due to low PTH
Secondary hypoparathyroid
27
Hypercalcaemia clinical picture
Polyuria, polydipsia, constipated, neuro confusion (seizures, coma - unlikely unless ca>3)
28
Hypercalcaemia aetiology dependent on
1) PTH suppression - Malignancy - humoral, bone mets, haem - Sarcoid (non renal 1a hydroxylation) - Vit D excess (sunbeds) - Thyrotoxicosis (thyroxine resorbs bone) - thiazide diuretics 2) PTH not suppressed = PTH regulatory problem - primary hyperparathyroidism
29
Hypercalcaemia tx
``` FLUIDS FLUIDS FLUIDS Bisphosphontes (IF CANCER ELSE NO) TX underlying cause ``` ``` Fluids = 0.9% saline Use frusemide (lose calcium in urine) ```
30
Causes of secondary hyperparathyroidism
Low ca --> High PTH Low vit D/ malabsorption CKD Pseudohypoparathyroid
31
What is Paget's disease
Focal bone remodelling - lytic and sclerotic lesions Warn, deformity, fracture, malignancy. Conductive and sensorineural hearing loss Disorder of bone turnover Skull and vertebrae aka axial 1) Osteolytic 2) Osteolytic-osteosclerotic 3) Quiescent osteosclerotic, Elevated ALP RAPID bone turnover on Nuclear med scan/XR Mosaic lines
32
Normal GFR
120ml/min | Above 90 is normal
33
Definition of renal clearance Use
Volume of plasma completely cleared of a marker substance.. per unit time Can be used to calculate GFR
34
Renal clearance formula
C=(UxV)/P ``` U= urinary conc of marker V = volume (needs to be /min so work out) P= plasma conc of marker ```
35
Conditions of a marker for renal clearance
1) Freely filtered by glomerulus 2) Not secreted/absorbed by tubular cells 3) Not bound to serum proteins
36
Gold standard marker for measuring GFR Limitation
Inulin - freely filtered, neutral charge, not processed by tubular cells Needs steady state infusion - research tool only
37
Endogenous markers of GFR
Urea - first - by product of protein metabolism - freely filtered by glomerulus - variable (30-60%) resorption by tubular cells - Highly dependent on nutrition, hepatic function and if GI bleed aka useless Serum creatinine - derived from muscle cells - Actively secreted into urine by tubular cells - Cr generation varies according to muscle, age, sex, ethnicity
38
What is eGFR Formula used to calculate Problem
To estimate creatinine clearance eGFR-EPI Takes into account age, sex, serum creatinine and ethnicity Still imprecise at higher GFRs
39
Alternative to serum creatinine for eGFR
``` cystatin C produced by all nucleated cells Constantly generated Freely filtered Almost completely reabsorbed and catabolised by tubular cells ```
40
What is the use os single injection GFR measurement
Pre chemo
41
Value of serum creatinine measurement
To determine change in renal function within an individual over time - trend more valuable than actual value.
42
What is measured on a urine dip
``` pH: 4.5-8 Specific gravity: 1.003-1.035 Protein Blood Leucocyte esterase: -ve result is significant Nitrite: detects bacteria, esp gram -ve ```
43
AKI with calcium oxalate crystals on urine microscopy | Dx
Ethylene glycol poisoning (aka anti-freeze) - was metabolised to glycolic acid - glycolic acid metabolised to oxalic acid - oxalic acid binds to calcium containing stones
44
Casts seen on urine microscopy indicated that the problem is where?
Glomerulus
45
Suspected renal stone - choice of imagine
CT-KUB Can do US-KUB after to look for hydronephrosis
46
Types of renal imaging
``` Plain KUB IVU CT US: Can differentiate CKD (shrivelled) and AKI/ look or hydronephrosis/ do a nephrostomy if kidney obstructed MRI Functional imaging - useful in paeds ```
47
AKI vs CKD
AKI - Abrupt GFR decline in days - Potensh reversible - Tx of precise diagnosis and reversing disease CKD - Longstanding decline in GFR - Irreversible - Tx to prevent complications and limit progression
48
AKI definition
Rapid reduction in kidney function, leading to an inability to maintain electrolyte, acid-base and fluid homeostasis
49
AKI stages
1: ↑ sCr by >26micromol/L OR 1.5-1.9x reference sCr 2: ↑sCr by 2.0-2.9 reference sCr 3: ↑sCr by >3 reference sCr, or increase by >354 micromol/L > means >/=
50
Causes of pre-renal AKI
``` True volume depletion - most common Hypotension Oedematous Selective renal ischaemia (RAS) Drugs affecting glomerular blood flow ```
51
Drugs that predispose to AKI
NSAIDs: Decrease afferent arteriole dilation Cacineurin inhibitors: Decrease afferent arteriole dilation ACEi/ARBs: Decrease efferent arteriole constriction Diuretics: Affect tubular function, decrease preload
52
What is ATN Management
Acute tubular necrosis Death of tubular cells - does not respond to restoration of circulating volume unlike pre-renal AKI Dialyse for 3 weeks, should recover
53
Intrisic renal AKI causes
Abnormality in ANY part of the nephron - Vascular disease: vasculitis - Glomerular: glomerulonephritis - Tubular: ATN - Interstitial: analgesic nephropathy
54
Mechanisms of direct tubular injury in AKI
- Mostly pre-renal AKI causing ATN - Endogenous toxins: Myoglobin/immunoglobuline - Exogenous toxins: contrast, aminoglycosides, amphotericin, acyclovir
55
Presentation of rhabdomyolysis induced AKI
Muscle weaknes | Dark urine + kidney injury
56
Rash (non-blanching, purpuric) + AKI
Systemic vasculitis
57
Immune dysfunction causing renal inflammation causes
Vasculitis Glomerulonephritis Dx on biopsy
58
Infiltration/abnormal protein deposition in AKI causes
Amyloidosis Lymphoma Myeloma
59
Post-renal AKI causes
Physical obstruction to urine flow - Intra-renal - Ureteric obstruction (bilateral) - prostate/urethral
60
What is obstructive uropathy | Pathophysiology
Hydronephrosis GFR depends on hydraulic pressure gradient. Obstruction increases tubular pressure Immediate decrease in GFR
61
Obstructive uropathy recovery
Immediate relief of obstruction restores GRR fully with no structural damage. But if prolonged, there is structural damage - Glomerular ischaemia - Tubular damage - Long term interstitial scarring
62
Measures for defining AKI severity
``` sCr as surrogate of GFR Urine output (needs full time nurse) ```
63
CKD stages
1: GFR >90 (norm) 2: GFR 60-89 mild 3: GFR 30 -59 mod 4: GFR 15-29 sev,, 5: GFR <15/dialysis ESRF
64
Worst outcomes in CKD
lowest GFR and higher albumin:Cr
65
Causes of CKD
``` Diabetes HTN Atherosclerotic renal disease Chronic glomerulonephritis Obstructive/infective urpoathy Polycystic kidney ```
66
Roles of the kidney
``` Excretion of water-soluble waste Water balance Electrolyte homeostasis Acid-base homeostasis Endocrine: EPO, RAS, vit D ```
67
Consequences of CKD
``` Hormonal function decline: - Anaemia - Renal bone disease Homeostatic decline - Acidosis - Hyperkalaemia CVD - Vascular calcification - Uraemic cariomyopathy Uraemia and death ```
68
Renal acidosis in CKD Tx
Metabolic acidosis - failing to excrete protons - -> Muscle and protein degradation - -> Osteopenia due to mobilization of bone Ca - -> Cardiac dysfunction Tx: oral sodium bicarbonate when serum bicarb <20
69
Hyperkalaemia in CKD
Potassium is major intracellular ion. Hyperkalaemia causes membrane depolarization, which is important in: - Cardiac function - Muscle function
70
Hyperkalaemia ECG changes
Peaked T waves Flattened P waves Broader QRS Can get tachy, VF, cardiac arrest
71
High potassium foods
Milk Choc Dried fruits Tomatoes
72
Anaemia of chronic renal disease
Progressive decline in EPO producing cells (necrosis) + loss of renal parenchyma Usually when GFR <30 Normochromic, normocytic anaemia Distinguish from other causes of anaemia that are common
73
Treatment of anaemia of CKD No response to tx: causes
ESA 1) Fe deficiency 2) TB 3) Malignancy 4) B12 and folate deficiency 5) Hyperparathyroidism
74
Real bone disease in CKD
Reduced bone density (osteopenia), bone pain and fractures - Osteitis fibrosa cystica - Osteomalacia - Adyndamic bone disease - Mixed osteodystrophy
75
Effect of CKD on PTH
CKD = phosphate retention --> increased FGF-23 (makes you pee it out) CKD also = decrease calcitriol --> hypocalcaemia >> sensed by parathyroid --> secondary hyperparathyroid Bone becomes more resistant to PTH Decreased Ca sensor Decreased calcitriol sensor
76
What is osteitis fibrosa X-ray features Histopath features
Occurs in HyperPTH (Can occur in CKD) Osteoclast resorption of caclified bone + replaced by fibrous tissue Trabeculae become larger - blackened bits on x-ray. Cystic?? Brown's tumours - many multinucleate giant cells
77
What is adynamic bone disease Tx
In CKD Excess suppression of PTH --> low bone turnover and reduced osteoid formation Can suppress PTH using vit D or phosphate binders
78
Tx of CKD bone diseases
``` Phosphate control - Diet + phosphate binders Vit D receptor activators - 1-alpha calidol (mainstay) - paricalcitol Dirtect PTH suppression - Cinacalcet ```
79
CVD in CKD mechanism
Most important consequence of CKD | - Risk of CVE directly predicted by GFR
80
Uraemic cardiomyopathy mechanism in CKD
LV hypertrophy LV dilation LV dysfunction
81
Contraindications to renal transplant
Active sepsis | Malignant disease within last 2 years
82
Normal pH on blood gas
7.35-7.45
83
Normal H+ in ECF
35-45nmol/l
84
Proton (H+) metabolism
Metabolism of fats, carbs and proteins produces carbon dioxide, water and hydrogen ions ~50-100mmol H+ produced per day Excreted by kidney
85
Buffering of hydrogen ions is by what
Bicarbonate (ECF, glomerular filtrate) Hb (RBC) Phosphate (Intracellular, Renal tubular fluid)
86
Metabolism of CO2
Metabolism of fat, carbs and proteins produces co2, water and hydrogen ions CO2 20,000-25,000 mol/day produced Excreted by lung
87
What is the main control of respiration
Chemoreceptors in the hypothalamic respiratory centre. | Any increase in CO2 stimulates respiration thus maintaining a stable conc. of CO2
88
Metabolic acidosis causes
Increased H+ production e.g. DKA Decreased H+ excretion e.g. renal tubular acidosis; renal failure Bicarbonate loss e.g. intestinal fistula
89
Uncompensated metabolic acidosis changes to ABG Compensated metabolic acidosis changes to ABG
High H+ Low bicarbonate High H+ Low bicarbonate Low CO2 - can’t compensate if resp failure - H+ will rise more
90
Acute Respiratory acidosis changes on ABG Chronic Respiratory acidosis changes on ABG
High CO2; high H+; high HCO3- High CO2; normalised H+; high HCO3- PH may be normal now
91
Respiratory acidosis causes
Poor ventilation Poor perfusion Impaired gas exchange If chronic COPD Emphysema
92
Causes of metabolic alkalosis
Hypokalaemia H+ loss e.g. pyloric stenosis, vomiting Ingestion of bicarbonate (tx for GI ulcer)
93
Cause of respiratory alkalosis
Hyperventilation - Anxiety - Hypoglycaemia
94
Aspirin overdose effect on ABG
Mixed metabolic acidosis and respiratory alkalosis Hyperventilation stimulated Hydrogen excretion by kidney
95
Haematuria causes
Nephritis - painless haematuria Subacute endocarditis - FUO and microscopic bacteriuria Acute rheumatic fever - child with sore throat Renal stones - pain
96
Biochem in primary hyperparathyroidism
High Ca, High/norm PTH, low Ph, high/norm ALP, norm Vit D
97
What are Looser's zones
Wide, transverse lucencies traversing part way through a bone - pesudofractures Associated with Vit D deficiency - osteomalacia
98
Primary hyperPTH symptoms
Moans - depression Stones - renal Groans - abdo pain, pancreatitis Bones - fractures
99
``` Radial cystic changes Browns tumours (what is it) Associated with what condition ```
Primary hyperPTH Brown's tumour = osteitis fibrosa cystica - many multinucleate giant cells
100
Hypercalcaemia symptoms
Moans, bones, groans, stones Asymptomatic Polyuria/polydipsia Band keratopathy (if present for long time e.g. primary hyperPTH) Complications: Osteitis fibrosa, pancreatitis, renal stones, peptic ulcer, skeletal changes
101
Which diuretic can you use in hypercalcaemia and which to avoid
``` Use frusemide (lose calcium in urine) Avoid thiazides (don't lose calcium in urine) ```
102
Hypercalcaemia tx
0.9% saline | frusemide in case of pulmonary oedema
103
What are purines
Ubiquitous biomolecules | Adenosine, guanosine, inosine
104
Roles of purines
Part of the genetic code (A and G) Second messengers for hormone action e.g. cAMP Energy transfer e.g. ATP
105
Purine catabolism
Purine --> Hypoxanathine --> xanathine --> urate --> Allantoin Step 2+3 requires XO Step 4 requires uricase (not in humans)
106
Challenges of excreting urate
Insoluble | Circulates at conc close to it's limit of solubility
107
Why is urate so close to it's limit of solubility in our body?
Tubular urate handing - reabsorbed, resecreted multiple times - ultimately only 10% secreted
108
Purine synthesis
``` De novo (less efficient, only norm occurring in BM where other pathway is insufficient) Salvage pathway: recycling - needs HGPRT (HPRT) ```
109
Rate limiting step of purine synthesis | Controls
Catalysed by PAT - Inhibition by ANP and GNP - Positive feedback by PPRP
110
IEM - Purine
``` Lesch Nyhan syndrome HGPRT deficiency Normal at birth 6/12 developmental delay Choreiform movements, spasticity, mental retardation Self mutilation ``` No ANP and GNP to inhibit PAT - de novo pathway goes into overdrive, more catabolism of inosinic acid --> urate levels build up in blood PPRP also builds up which drives PAT
111
Thiazide diuretics may cause what on bloods
Hypocalcaemia Hyponatraemia Hypoglycaemia Hyperuricaea
112
Gout crystals are Diagnosis
monosodium urate Tap effusion Polarised light Red filter Negatively birefringent needles perpendicular to axis of compensation
113
Gout acute vs chronic
``` Podagra - acute arthropathy vs Tophaceous gout - chronic build up - periarticular - ear lobes and hands ```
114
Acute gout tx
NSAIDs - reduce inflammation e.g. diclofenac but avoid in CKD, asthmatics, peptic ulcer disease Colchicine - inhbits microtubule formation, inhibiting neutrophil motility, can't get into joints and react to presence of urate crystals Glucocorticosteroids - anti-inflammatory DO NOT BRING DOWN URATE LEVELS ACUTELY
115
Non-acute gout tx
Water, stop alcohol, reduce dietary urate (sardines, liver) Reverse causing factors e.g. diuretics Allopurinol inhibits XO Increase renal excretion of urate with a uricosuric e.g. probenecid
116
Allopurinol used for MOA Contraindications
non-acute gout Inhibits XO - reduces urate production Azathioprine (az metabolite is metabolised by XO - can render patients neutropenic)
117
NSAID cautions/CI
Toxic to kidneys - avoid in CKD | CI in asthmatics and peptic ulcer
118
Pseudogout crystals | Dx
Pyrophosphate Knee and shoulder Tap effusion Polarised light Red filter Positively birefringent needles parallel to axis of compensation
119
Hyponatraemia cut off
<135mmol/L
120
Pathogenesis of hyponatraemia
Almost always due to excess water (extracellular) with no change in Na so conc is lower
121
Hormone controlling Na levels
ADH (vasopressin)
122
ADH action
Acts on collecting ducts on V2 receptors Insertion of aquaporin 2 Water reabsorption If high conc, will also act on V1 receptors - vasopressor effects (smooth muscle)
123
What stimulates ADH secretion
1) High serum osmolality detected by hypothalamic osmoreceptors 2) Low blood volume/pressure detected by baroreceptors in carotids, atria, aorta
124
1st thing to do in a patient with hyponatraemia
Clinical assessment of volume Urine sodium - low is most reliable sign of hyponatraemia Hypovolaemia: Dry mucus membranes, decreased skin turgor, JVP not visible Hypervolaemia: Peripheral oedema, raised JVP Difficult to distinguish between hypovolaemic and euvolaemic patients
125
Signs of hypovolaemia
``` Tachycardia Postural hyptension Dry mucus membranes Reduced skin turgor Confusion/drowsy Reduced UO Low urine Na <20 ``` DO URINE SODIUM (kidneys reabsorb water and salt when hypovolaemic)
126
When in hyponatraemis is urine sodium not helpful
Pts on diuretics - have to stop diuretics before checking
127
Causes of hyponatraemia in hypovolaemic changes
Extra renal: d+V --> fluid loss --> hypovolaemia --> barorecepters stimulate --> ADH increased --> water resorption --> hyponatraemia Renal: Diuretics will cause hyponatraemia ONLY when recenly started
128
Hypervolaemia clinical signs
Raised JVP Bibasal crepls Peripheral oedema
129
Causes of hyponatraemia in hypervolaemic pts
Failure 1) HF: Reduce CO --> Low BP --> excess ADH --> too much water 2) Cirrhosis: Patients vasodilate (due to NO) --> lower BP --> increase ADH 3) Renal failure: not excreting water
130
Causes of hyponatramia in euvolaemic patients
All Endo 1) Hypothyroid: Reduced cardiac contractilty, reduces CO --> low BP --> ADH 2) Adrenal insufficiency: May cause hypovolaemia or pt may be euvolaemic because they need water for cortisol excretion 3) SIADH
131
SIADH causes
``` Any CNS pathology Any lung pathology Tumours - any Post-surgery Drugs (SSRI, TCA, opiates, PPI, carbamazepine) ```
132
SIADH effect on sodium and osmolality
Excess ADH - retain more water - detected by atria - ANP release --> natriuresis (lose sodium and excess water with that) - euvolemic Low plasma osmolality (~275-295mmol/kg) High urine osmolality (>100)
133
SIADH electrolyte abnormality and fluid status
Low Na Euvolaemic More ADH - retain water Atria detects BP - natriuresis (lose Na and excess water)
134
SIADH dx
No hypovolaemia No hypothyroidism No adrenal insufficiency Reduced plasma osmolality Increased urine osmolality (>100)
135
SIADH tx
Do NOT give saline - will decrease sodium more --> fits --> death - Fluid restrict Demecleocycline - reduces responsiveness of CDT cells to ADH Tolvaptan: V2 receptor antagonist Can also use a combination of salt and loop diuretic
136
Treatment of hyponatraemia
If hypovolaemic - replace with 0.9% saline - Ensure NOT SIADH If hypervolaemic - Fluid restrct - Tx underlying cause If euvolaemic - Fluid restrict - Tx underlying cause - Exclude tumour - head and chest imaging, examine, inc breast
137
Treatment of severe hyponantraemia
ONLY IF reduced GCS and fitting - Tx seizures - Expert help - Hypertonic saline (2.7%)
138
Hypernatraemia cut off
>145
139
Hypernatraemia causes
Water loss not replaced - GI, sweat - Renal loss - osmotic diuresis (DM uncontrolled), reduced ADH release/action (DI) Patient can't control water intake e.g. child/elderly - safeguarding issue
140
Diabetes insipidus symptoms
Polyuria | Polydipsia
141
Investigating diabetes insipidus
Serum glucose: Exclude DM Serum K: Exclude hypokalaemia Serum Ca: Exclude hypocalcaemia Altered Ca and K can cause nephrogenic DI (kidney resistant to ADH actions) ``` Plasma and urine osmolaltity WATER DEPRIVATION TEST normal: urine will concentrate DI: Won't concentrate urine (<300) (Nephrogenic will not concentrate even with desmopressin) ```
142
Hypernatraemia tx
Fluid replace with water ideally (dextrose if acute) If hypovalaemic - 0.9% to correct ECF depletion - Dextrose to correct water deficit Serial Na measurements every 4-6hours Tx underlying cause
143
Hallmarks of inherited metabolic disorders
Lack of end product Build up of precursors Abnormal, toxic metabolites
144
What is phenylkotenouria
Phenylalanine hydroxylase deficiency - build up of phenylalanine in blood IQ <50 (toxic to CNS)
145
Which IEM associated with low IQ Test Tx
Phenylketonuria IQ<50 Blood Phe Effective tx if started early in 1st 6 weeks of life
146
What is sensitivity
True positive/Total disease present
147
What is specificity
True negative/Total disease absent
148
PPV
Positive predictive value | True positive/Total positive
149
NPV
Negative predictive value | True negative/total negative
150
PPV for PKU
80%
151
Congenital hypothyroidism newborn screening Based on PPV
Based on high TSH | PPV 60-70%
152
Cystic fibrosis affects which organs Where is defect Newborn dx
Lungs: recurrent infections Pancreas: malabsorption, steatorrhoea, diabetes Liver - cirrhosis Transmembrane conductance regulator High blood immune reactive trypsin
153
What is MCADD Newborn screening
Medium chain AcylCoA dehydrogenase - Fatty acid oxidation disorder No acetyl coA produced - needed for TCA cycle - needed for ketone production Screening acylcarnitine levels by tandem MS Cot death - go to sleep, can't break down fat, dies of hypoglycaemia
154
Homocystinuria presentation
IEM Lens dislocation Mental retardation Thromboembolism
155
Osmolarity equation
2(Na+K) + urea + glucose
156
Anion gap formula Normal anion gap
Na+K - Cl - bicarb ~14-18mmol/l
157
T2DM dx IGT
Fasting > or = 7mM OGTT > or = 11.1 HbA1c: 6.5% (48) Glucose tolerance test - 75g glucose given - Diabetes = >11.1mM at 2h - IGT = 7.8-11.1 at 2h (fasting <7)
158
Body response to hypoglycaemia (normal)
1. Insulin suppression 2. Glucagon release 3. Adrenaline release 4. Release of cortisol FFA undergo beta oxidation in mitochondria to provide energy (ketone by products) - ketones, FFAs and glucose increase
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Investigations in acute hypoglycaemia pt
Measure and confirm it is hypoglycaemia Urine ABG Continuos glucose monitoring over 7 days when not acute
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Hypoglycaemia causes in diabetics
Medications 1) Oral hypoglycaemic - Sulphonlyureas, Meglitinides (short acting sulfonylureas), GLP-1 agents (exanatides) 2) Insulin - Rapid acting (with meals), long acting (hypos at night/between meals) 2) Other drugs - beta blocker, salicyclates, alcohol SGLT1 inhibitors can also make people hypoglycaemic
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Hypoglycaemia causes in non-diabetics
``` Critically unwell Organ failure Hyperinsulinaemia Post-gastric bypass Extreme weight loss - anorexia with poor liver glycogen stores ```
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Blood tests to differentiate causes of hypoglycaemia
``` Insulin C-peptide - marker of endogenous insulin - Drug screen Auto-antibodies Cortisol/GH FFA, blood ketones Lactate ```
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Hypoglycaemia with low insulin and low c-peptide causes
Appropriate response to hypoglycaemia - Fasting/starving - Strenuous exercise - Critically ill - Endocrine deficiencies : Hypopituirary, Adrenal failure - Liver failure - failure of glycogenesis and glycogenolysis
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Neonate hypoglycaemia causes
Pathological If no ketones - IEM - FFA raised, low ketones - MCADD, FAOD, GSD type 1 If ketones - IEM - FFA raised, raised ketones - MSUD, GH deficiency, Galactosoaemia Explainable - premature, co-morbidities, IUGR, SGA - Inadequate glycogen and fat stores - Should improve with feeding
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Hypoglycaemia, high insulin, high C-peptide | Next investigations
Sulphonylurea drug screen - If negative - Insulinoma (MEN1). Tx = resection
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Sulphonylureas mechanism of action
Bind to K+ channels and force them to close --> Calcium entry Insulin secretion independent of glucose Normally: Glucose goes down glycolytic pathway, produced ATP, which closes K+ sensitive ATP channels --> K+ can't leave cell --> membrane depolarises and Calcium enters --> insulin secretion
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Hypoglycaemia, high insulin, low c-peptide cause
Factitious insulin usage
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Hypoglycaemia - persists with tx, undetectable insulin and C peptide, undetectable FFA and negative ketones Cause
Non-islet cell tumour hypoglycaemia - mesenchymal/epithelial tumours - Producing IGF-2 that binds to insulin receptor, switches off own insulin and ketones and FFAs not produced
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Hypokalaemia causes
1) Intestinal loss - D&V, fistula 2) Renal loss - Mineralocorticoid excess (always in ectopic ACTH), - Diuretic - Renal tubular disease - Conn's (hyperaldosteronism) - Osmotic diuresis (uncontrolled DM) 3) Redistribution - insulin, alkalosis
170
What does zona fasiculata make?
Cortisol | Glucocorticoid
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Zona glomerulosa or fasiculata - which is thicker
Fasiculata - make more cortisol than aldosterone
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``` Low T4 (<5) High TSH (>50) Dx ```
Primary hypothyroidism
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Primary hypothyroidism + Addisons =
Schmidt's syndrome now called PGAS T2 (polyglandular autoimmune syndrome type 2)
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Test for Addison's disease
Short Synacthen - measure cortisol and ACTH at start - give 250 microgram synthetic ACTH by IM - Check cortisol at 30 and 60 minutes Addison's ACTH>100, cortisol <10nM in both
175
Glucose tolerance test used to diagnose what
Acromegaly | Diabetes
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Acromegaly test
Glucose tolerance test - Measure GH - in normal it will be suppressed - In acromegaly - GH fails to supppress
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HTN adrenal mass differentials
Phaeochromocytoma (tumour secreting adrenaline) Conn's syndrome (tumour secreting aldosterone) Cushing's syndrome secretes cortisol
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High urinary catecholamines Dx Management
Phaeochromocytoma Urgent alpha blockade with phenoxybenzamine Fluid with this so they don't go into shock Beta blocker next day (for reflex tachycardia) Then arrange surgery
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What is a phaeochromocytoma
Adrenal medullary tumour that secretes adrenaline and can cause severe HTN, arrhythmia and death
180
Phaeochromocytoma associations
MEN2 NF1 Von Hippel Lindau
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High sodium, low K, aldosterone raised, renin lowered
Primary hyperaldosteronism aka Conn's syndrome Important to do test if HTN and young!!
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T2 DM obese F HTN, bruising, high Na, low K+ Aldosterone low, renin low
Cushing's syndrome Conn's excluded by aldosterone low
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Best tests for Cushing's syndrome
Midnight cortisol (if asleep) high - but can't be done on someone that is ill as they will have a high cortisol Dexamethasone is dynamic test - cortisol not suppressed in Cushing's syndrome
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Causes of Cushings
1) Steroids 2) Pituitary dependent Cushing's disease (85%) 3) Ectopic ACTH 4) Adrenal adenoma
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Cushing's syndrome on low dose dexamethasone test | - what's next
Sample from pituitary (IPSS) NOT high dose dexamethasone - as good as a guess
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Normal potassium
3.5-5mmol/L
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Which hormones regulate renal potassium
Angiotensin II | Aldosterone
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What stimulates aldosterone
ang-2 | K+ high
189
Aldosterone effect on Na conc
NONE | Na and water in
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Where dose aldosterone act
Principal cells in cortical collecting tubule - binds to mineralocorticoid receptor - expression of epithelial sodium channels - as sodium reabsorbed, lumen becomes -ve - k moves down electrical gradient
191
Causes of hyperkalaemia
1) Excessive intake - oral, parenteral, stored blood transfusion 2) Transcellular movement - Acidosis - Rhabdomyolysis - DKA (treakment with insulin will drop K) - malfunctioning valves 3) Decreased excretion - AKI (oliguric phase) - CKD - K sparing diuretics (spironolactone) - Addison's - ACEi, ARBs, NSAIDs Could also be delayed separation - delay in separating the cells in the blood sample from the serum, so some cells break down and release potassium, causing a falsely high potassium level
192
Management of hyperkalamia
10ml 10% calcium gluconate 100ml 20% dextrose + 10 units insulin Nebulized salbutamol Tx underlying cause
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Hypokalaemia causes
1) GI loss/ low intake - D+V - Anorexia (+ laxative use) - Fasting/diet 2) Renal loss - In ascending LOH: loop diuretics/ Bartter syndrome - In DCT: thiazide diuretic/Gitelman syndrome - Hyperaldosteronism - --> can be tumours, ectopic ACTH as cortisol binds to MR - Osmotic diuresis 3) Redistribution into cells - Insulin - beta-agonists - alkalosis Rare: renal tubular acodosis 1 + 2, hypomagnesia
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Clinical features of hypokalaemia
muscle weakness cardiac arrhythmia polyuria, polydipsia (DI)
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Screening of hypokalaemia
Aldosterone:Renin ratio | For Conn's
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Hypokalaemia management
Oral SandoK and monitor If < 3 IV potassium chloride Max rate 10mM/hr - Rates higher irritate peripheral veins Tx underlying cause
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Elevated TSH, Normal T4, TPO antibodies
Subclinical hypothyroidism with risk of later clinical hypothyroidism
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Tired | T4 normal, TSH normal
Euthyroid
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Low T4, High TSH
Primary hypothyroidism
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High thyroglobulin
Used to screen for recurrence of differentiated thyroid carcinoma
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High calcitonin
To screen for medullary thyroid carcinoma
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Pituitary hormones controls
``` GH - GHRH Prolactin - TRH; Dopamine -ve ACTH - CRH TSH - TRH FH, LSH - GnRH ```
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Increased skull/head size, deafness, high otput cardiac failure, bone pain, microfractures Biochem
Paget's disease Only ALP high
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Causes of primary hyperparathyroidism
90%: Parathyroid adenoma | Rest: Chief cell hyperplasia
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Aldosterone mechanism of action
binds to MR in cortical collecting tubes. Serum glucocorticoid kinase expressed, phosphorylates nedd4 (normally degrades sodium channels) -> sodium re absorption increased -> -ve lumen -> potassium moves down electrical gradient Na conc not affected as water follows it
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Metabolic acidosis effect on K+
Hyperkalaemia
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Raised anion gap causes and cuttoff
>18mmol/l K: etocidosis U: raemia (renal failure) L: actic acidosis T: oxins (ethylne glycol, methanol, paraldehyde, salicyclate)
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Liver functions
``` Intermediary metabolism Protein synthesis Xenobiotic synthesis Hormone metabolism Bile synthesis Reticulo-endothelial ```
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What is intermediay metabolism in liver
``` Glycolysis Glycogen storage Glucose synthesis Amino acid synthesis Fatty acid synthesis Lipoprotein mtabolism ```
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Liver function tests
Synthetic function - Albumin - Clotting - PT - Glucose Liver cell damage markers - ALT - AST - GGT - ALP - Bilirubin AFP - tumour market
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Elevated AST/ALT ration
Suggestive of alcoholic liver disease or advanced fibrosis/cirrhosis in absence of alcohol use Aspartate transaminase (AST) also raised in - HCC - Hepatitis - MI - Acute pancreatitis - AKI
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Elevated GGT
Chronic alcohol use Also slightly up in bile duct disease and hepatic mets
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Markedly elevated ALP causes
Obstructive jaundice or bile duct damage Less elevated in viral hepatitis or alcoholic liver disease + Bone disease (mets and pregnancy) ALP is in high concentration in liver, bone, intestine and placenta >5 x normal: Bone (Paget's, osteomalacia), liver (cholestasis, cirrhosis) <5 x normal: \bone (tumours, fractures, osteomyelitis), liver (infiltrative disease, hepatitis)
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Low albumin causes
Sepsis, shock - most common Reduced production - chronic liver failure, malnutrition Loss - kidney/ GI
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Alpha feto protein (AFP) elevation causes
HCC tumour marker Pregnancy, testicular cancer
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Approach to jaundice (raised bilirubin)
Normal ezymes - Haemolysis - Gilbert's ALT/AST: hepatocellular - acute - Chronic AST: Cholestatic - Dilated ducts = obstruction e.g. cancer, gallstones - Undilated ducts = drugs/PBC-PSC, pregnancy etc - do liver screen Unconjugated vs conjugated v rarely measured clinically
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After US and abnormal LFTs, liver screen tests
``` CK, TFTs, fasting lipids, fasting glucose Hepatitis serology Coeliac serology Alpha-1-antitrypsin Ceruloplsmin (<50y) Liver AAbs (LKM, aSMA, AMA Immunoglobulins Ferriin ```
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Isolated ALT increase
Think fatty liver disease if 3 times norm (norm =40)
219
Drug causing cholestasis cholestasis LFTs
Augmentin ALP markedly high
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Courvoisier's sign
Painless palpable gall bladder, jaundice unlikely to be caused by gall stones
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ALT > 1000
Only 3 causes 1) Toxins (e.g. paracetamol) 2) Viruses 3) Ischaemia
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Endocrine risk if obstetric bleed How to manage and prevent this risk
Pituitary infarction as big andslightly ischaemic in pregnancy ALA Sheehan syndrome - loss of pituitary hormone function - Tired - no ACTH or TSH - normal BP - No return of periods Syntocinon, ergometrine and antibiotics
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Galactorrhoea - what nvestigation to do
Prolactin (>600 is high) >6000 = prolactinoma Should also do pituitary function testing - LHRGH, TRH, Hypoglycaemia - - insulin for hypo (<2.2) increases CRF and GHRH
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Assessing pituitary function
``` CPFT method Fast overnight, IV access 0.15 units/kg insulin 200mcg TRH 100mc LHRH ``` Measure glucose, cortisol, GH, LH, FSH, TSH and prolactin every 30 mins Normal - GH reaches 10, cortisol reaches 550, glucose <2.2 and then recovers after 30min
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Prolactinoma treatment
Bromocriptine or cabergoline | Dopamine agonist
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Acromegaly treatment
1) pituitary surgery - curative 2) radiotherapy 3) Cabergoline 4) Octreotide
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Hyponatraemia, hypokalaemia Hypoglycaemia Cause: WW = TB
Addison’s disease Cause: WW = TB Illness increases need for steroids
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Hyponatraemia, hypokalaemia Hypoglycaemia Primary hypothyroid
Schmidt’s syndrome - PGAS T2
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Addison’s disease signs and test
Hyponatraemia hyperkalaemia Short synacthen test - measure acth and cortisol at beginning - 250mcg ACTH IM - check cortisol at 30 and 60mins In Addison’s - cortisol <10 at both 30 and 60 mins
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Addison’s signs
Low BP/ postural hypotension Pigmentation/tan Fluids Hydrocortisone Thyroxine last
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Adrenal mass differential
Conn’s Cushing’s Pheo
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Cushing’s test Give all even though not used anymore
Cortisol 12 midnight (don’t stop making in Cushing’s) Dexamethasone suppression test - not suppressed in Cushing’s Cushing's Syndrome caused by an adrenal tumour/ ectopic ACTH - low dose: no change - high dose: NO CHANGE Cushing's Disease: - low dose: no change - high dose: NORMAL SUPPRESSION
233
Conn’s what is it | Treatment
Primary hyperaldosteronism Surgery - find tumour
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Cushing’s syndrome causes
Oral steroids Pituitary dependent Cushing’s disease Ectopic ACTH Adrenal adenoma
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Cushing’s syndrome as cortisol not suppressed by dexamethasone Next step
Sample from pituitary - majority pituitary
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What is porphyriasis
7 disorders caused by deficiency in enzymes, involved in haem biosynthesis —> build up of toxic haem precursors
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Acute intermittent porphyriasis type of inheritance and what is it
Porphriasis = group of disorders with deficiency of enzymes involved in haem biosynthesis so get build up of toxic haem precursors AIP = deficiency of hydroxymethylbilane (HMB) synthase Autosomal dominant Neurovisceral symptoms only. No cutaneous manifestations Dx ALA + PBG in urine (port wine urine) Precipitated by ALA synthase inducers (steroids, ethanol, barbiturates), stress (infection,surgery), reduced calorie intake, premenstrual Treatment - avoid precipitating factors, analgesia, IV carbonate/haem arginate
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What is acute porphyriasis with skin lesions Inheritance
Hereditary coproporphyria (HCP) and Variegate porphyria (VP) Autosomal dominant Neurovisceral and skin lesions Deficiency in corpoporyphrinogen oxidase or protoporphyrinogen oxidase Raised porphyrins in faeces and urine
239
Non-acuteporphyriasis type
Skin lesions only CEP (congenital erythropoietic porphyria) EPP (erythropoietic protoporphyria) PCT (porphyriasis cutanea tarda) EPP Photosensitivity, burning, itching oedema after sun exposure Deficiency in ferrochetelase PCT Inherited/acquired Urophorphyrinogen decarbocxylqse deficiency Cutaneous symptoms of vesicles on sun exposed sities Dx: urinary uroporphyrins + coproporphyns + ferritin Tx: avoid precipitants (alcohol, hepatic compromise, phlebotomy)
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Combined pituitary function test Method Results Contraindications
Give insulin, GnRH, and TRH. Measure levels at 0, 30, 60, 90, 120 mins 1) insulin — adequate cortisol response = > 170 to above 500nmol/l — norm GH response = > 6mcg/l 2) TRH — norm = TSH rise to >5 (30min > 60min) Hyperthyroid = TSH remains suppressed Hypothyroid = exaggerated response 3)GnRH — norm = Peaks at 30 or 60 mins. LH > 10, FSH > 2
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Bloods findings in Addison’s disease Examination findings Test to do Treatment
Hyponatraemia hyperkalaemia Hypoglycaemia Low BP, pigmentation Short SynACTHen test In Addison’s - cortisol < 10nM at 30 and 60 min Treat with fluids (saline), hydrocortisone, then lastly thyroxine ?
242
Adrenal mass differentials
Phaeo Cushing’s syndrome Conn’s syndrome
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Cushing’s test Cushing’s causes
Dexamethasone test. In Cushing’s - cortisol is not suppressed If high - sample from pituitary next Most oral steroids 85% Cushing’s disease Ectopic ACTH Adrenal adenoma (10%)
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Vit A deficiency clinical picture excess clinical picture
Deficiency = colour blindness Excess = exfoliation hepatitis
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Vit D deficiency clinical picture Excess clinical picture
Deficiency = osteomalacia/rickets Excess = hypercalcaemia
246
Vit E deficiency clinical picture
Deficiency = Anaemia, neuropathy, ? Malignancy, IHD Excess = none
247
Vitamin K deficiency clinical picture Test
Defective clotting PTT
248
B1 deficiency Clinical picture Test Management
Beri beri Neuropathy Wernicke syndrome RBC transketolase Replace thiamine. No test needed usually
249
B2 deficiency clinical picture
Glossitis
250
B6 deficiency clinical picture Excess clinical picture
``` B6 = pyridoxine Deficiency = dermatitis / anaemia ``` Excess = neuropathy
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B12 deficiency clinical picture
Pernicious anaemia Other autoimmune conditions - thyroid/T1DM
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Folate deficiency clinical picture
Macrocytic anaemia | Neural tube defects
253
Niacin deficiency clinical picture
Diarrhoea, dementia, dermatitis and ultimately death
254
Iodine deficiency clinical picture
Hypothyroid
255
Fluoride deficiency clinical picture Excess clinical picture
Dental caries Fluorosis
256
High amylasse
Acute pancreatitis - usually >10 x normal upper limit Smaller increases in other acute abdomen states Salivary isoenzyme also exists
257
CK forms
MM- skeletal muscle MB 1+2: Cardiac muscle BB: Brain - activity minimal even in severe brain damage
258
Raised CK causes
Rhabdomyolysis ``` Muscle damage due to any cause Myophathy (DMD) - >10 x ULN MI (>10 x ULN) Severe exercise ( 3 x ULN) Physiological - Afro Caribbean (<5x ULN) ```
259
Dx criteria for MI biomarkers
Troponin typical risk and gradual fall (marker of choice for MI) More rapid rise and fall of CK-MB AST + LDH also raised ``` + At least one of: Ischaemic symptoms Pathological Q waves on ECG ECG changes indicative of ischaemia Coronary artery intervention ```
260
HF biomarker
ANP | Best = Brain natriuretic peptide
261
39yo F, BMI 43 has elevated ALP and RUQ pain. What other enzyme can you measure to confirm dx
GGT (gamma glutamyl transferase)
262
Hypoglycaemia definition
<3.4mmol/L at imperial
263
hypoglycaemia symptoms
Adrenergic - tremors, sweating, palpitations, hunger Neuroglycopenic - Somnolence, confusion,inco-ordination, seizures, coma Or none
264
Which scan for bone density in hyperparathyroidism
Radius - DEXA
265
Which scan for bone density in steroid exposure?
hip and back and also for post-menopausal osteoporosis | DEXA
266
LVH causes
HTN | Aortic stenosis
267
ST elevation in leads II, III, aVF Diagnosis Which part of heart affected
Inferior wall MI | Supplied by RCA
268
drug that inhibits the enzyme dipeptidyl dipeptidase IV (DPP-4)
Gliptins
269
MEN syndromes
MEN1: pituitary, parathyroid, pancreas MEN2a: parathyroid, phaeo, medullary thyroid MEN2b: phaeo, medullary thyroid, mucosal
270
Check for recurrence of papillary thyroid cancer
Thryoglobulin
271
Hyperthyroid causes Treatment
Graves Toxic multinodular Goitre Single adenoma Lower uptake on scan Thyroiditis Post patrum thryoiditis Others Silent/facticous thyrodititis TSH induced Thyroid cancer induced Dx by low TSH, high T3/4, Tch sncan, antibodies Beta block if >100 HR Radioiodine. Only if not working: Carbimazole, propylthiouracil as rare risks of agranuolcytosis
272
Types of thyroid cancer Treatment
Papillary (>60%) - psammoma bodies Follicular Medullary (Men 2A) - calcitonin producing. Originates in parafollicular cells Surgery +/- Radioiodine + Thyroxine (to reduce TSH)
273
Hypothyroid causes
Hashimoto's (TPO antibodies) Atrophic Post Surgery/radioiodine Drugs - lithium, amiodarone
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Thyroid phsyiology
Iodide uptake into thyroid actively TPO coverts back to iodine TG takes up iodine and converts to thyroxine (2 iodone form DIT and eventually thyroxine) T4 stored in thyroid gland. All controlled by TSH
275
Thyroxine in periphery
T4 TBG-T4 75% TBPA-T4 20% Albumin-T4 - 5% fT4 0.03%
276
Troponin after MI
Rises 4-6h post MI Peaks 12-24h post MI Remains elevated for 3-10 days
277
Why might TPMT be measured
Prior to azathioprine use
278
Hyperammonia newborn red flags for the condition
Condition = Urea cycle disorder (in liver to detoxify ammonia) Vom, no diarrhoea Resp alkalosis Hyperammonia - v toxic. 1 day exposure = coma + IQ shutdown Neurological encephalopathy Rx: Stop feeds, 10% dextrose Get rid of ammonia with sodium benzylate or sodium phenylacetate Dialyse
279
``` Newborn with Vomitin + Diarrhoea Conj hyperbilirubinaemia Hepatomegaly Hypoglycaemia SEPSIS ```
Galactosaemia = carbohydrate disorder
280
Cholesterol absorption
Diet (EGGS) but Comes mainly from bile. Transported across intestine by NPC1L1 (ABC G5/8 are reverse). Bile reabsorbed in ileum In liver, downregulates HMG coAr eductase (-ve feedback) 2 paths for cholesterol in liver 1) Hydrolysed into bile acids 2) Esterified by ACAT and with TG and apoB incorporated into VLDLs (MTP control) CETP mediates - Cholesterol from HDL to VLDL - TG from VLDL to HDL ABC 1A mediates - HDL pick up of excess peripheral cholesterol LDL transports cholesterol to periphery
281
Triglyceride transport and metabolism
Source = fatty foods that are hydrolysed and broken into fatty acids Fatty acids resynthesised to TG and taken up by chylomicron Chylomicrons are hydrolysed to FFAs FFAs taken up by liver and adipose tissue Liver resynthesises FFAs into TG and exports to VLDL
282
Primary hypercholesterolaemia Mutations Presentation Management
Dominant mutations of LDL receptor (Or apoB, PCSK9 genes) - coronary disease risk 10x increased Homozygote: Arcus, atheroma of aortic root <20yo Hetrozygote: Arcus later, xanthelasma, tendon xanthelasma PCSK9 function is to bind LDL receptor and degrade Gain of function mutation = LDL receptor degraded --> high LDL Evolocumab (PCSK9 mAb)
283
Diabetes treatment
Start with metformin Then GLP-1 analogue (Exanatide) or basal insulin If long standing poorly controlled T2DM with heart disease consider: - Empaglaflozin - Liraglutide (GLP-1 analogue) GLP-1 secreted from gut and signals pancreas to make insulin Empagliflozin = SGT2 inhibitor = makes you pee out protein
284
Primary hypertriglyceridaemia
1: lipoprotein lipase deficiency or apoC II deficiency - eruptive xanthomas - Cream floats to top of plasma IV: Increased TG synthesis - Cream doesn't float to top but get VLDL V: More severe version of type IV - Mix of chylomicrons and VLDL on plasma test
285
A 60-year-old woman with hypothyroidism presents with progressive dyspnoea and tiredness. FBC reveals macrocytic anaemia.
Probably B12 deficiency because autoimmune Check parietal cell antibodies
286
Albumin levels vary with
Posture and so does renin - Rises in the upright position. - Some people have so-called benign postural and/or exercise-induced albuminuria.
287
Digoxin toxicity features
Arrhythmia: the most common arrhythmias are ventricular extrasystoles, ventricular bigeminy / trigeminy and atrial tachycardia with complete heart block Anorexia, nausea and vomiting and occasionally, diarrhoea Confusion especially in the elderly Yellow vision (xanthopsia), blurred vision and photophobia Symptoms of under-treatment and toxicity may be similar
288
Lipid soluble drug metabolism by the liver
1) Oxidation by cytochrome p450 | 2) Conjugation by sulphate/gluconaride
289
Lithium levels are affected by
Any diuretics NSAIDS ACEi/ARBs Dehydration
290
Substance missuse Cyanide poisoning presentation Heroin overuse presentation Aspirin (salicyclate) Ecstasy
Dead - brick red and almond smelling Heroine: ARMED - C: Respiratory depression. +ve 6MAM urine test Aspirin: Metabolic acidosis, repiratory alkalosis late presentation. Haeomodialyse Ecstasy: Wide dilated pupils, agitated TCAs: Wide dilated pupils, drowsiness, hyperreflexia, widened QRS
291
Activated charcoal use
Generally if within an hour of taking Not for use in poisoning with cyanide, iron, ethanol, lithium, acid or alkali, pesticides
292
How to assess long term drug use Best quick and cheap test for drug use
Hair sample Saliva
293
A 65 year old female presents to her new GP 5 years after an operation on her abdomen. She cannot remember the details of the operation but does remember that she was suffering from severe Cushing's Disease at the time. She now notes a progressive 'tanning' of the skin
Nelson Syndrome Old days, patients who had pituitary Cushing's had bilateral adrenalectomy as a treatment option. This would leave the pituitary adenoma free to grow, and the ACTH would continue to rise. In addition POMC levels (precursor to ACTH) would rise too. This would make patients become more tanned. The pituitary tumour would get larger, and eventually cause real local problems, originally described by Nelson
294
A 27 year old woman presents with a three month history of weight gain, deepening voice and secondary amenorrhoea. Examination reveals clitoromegaly, acne, greasy skin and hirsutism. Serum cortisol is grossly elevated and ACTH levels are undetectable.
Adrenal carcinoma because primary hyperaldosteronism
295
CAH
21-Hydroxylase Deficiency is most common cause (CYP21) Diagnosis: High 17-Hydroxyprogesterone in serum Hyponatreamia with Hyperkalaemia

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