Biochemistry AS Flashcards
What would you see on bloods in dehydration?
Increased urea, creatinine
Increased albumin
Increased haematocrit
Disproportionately increased urea to creatinine.
What would you see in a low GFR?
Increased Urea Increased Creatinine Increased H+ Increased Potassium Increased PO4 Decreased Ca
Tubular dysfunction
Normal U and Cr
Decreased K, decreased Urate, decreased PO4, decreased HCO3.
What would you see in thiazide and loop diuretics (furosemide)
Decreased Sodium
Decreased Potassium
Increased HCO3
Increased Urate
Hepatocellular Disease views?
ETOH = AST:ALT>2, increased GGT
Viral = AST: ALT <2
Increased bilirubin, increased ALP, decreased albumin, increased PT (APTT increased if end-stage).
Cholestasis on blood test?
Increased ALP, increaseD GGT, increased bilirubin, increased AST.
Excess EtOH intake blood test levels?
Increased GGT, Increased MCV, evidence of hepatocellular disease.
Addison’s disease bloods?
Increase potassium, decreased Na
Cushing’s Disease bloods?
May show: decreased K, Increased sodium, increased HCO3
Conn’s disease bloods?
Decreased K
Increased Na
Increased HCO3
Diabetes insipidus bloods?
Increased sodium
Increased serum osmolality
Decreased urine osmolality
SIADH bloods?
Patient presents with hyponatraemia, then to check osmolality of the urine,
Decreased sodium
Decreased serum osmolality
Increased urine osmolality
Increased Urine Na
Hyponatremia - levels and symptoms
<135: n/v, anorexia, malaise
<130: headache, confusion
<125: seizure, non-cardiogenic pulmonary oedema
<115: coma and death
What are the causes of hypovolaemic hyponataemia
U Na > 20nM (= renal loss)
- Diuretics
- Addison’s
- Osmolar diuresis (e.g glucose)
- Renal failure (diuretic phase)
U Na < 20mM (extra-renal loss)
- Diarrhoea
- Vomiting
- SBO
- Burns
What are the causes of hypervolaemic hyponatraemia
Cardiac failure
Nephrotic syndrome
Cirrhosis
Renal failure
Euvolaemic hyponatraemia?
U osmolality >500 - SIADH
U osmolality <500 - Water overload, severe hypothyroidism, glucocorticoid insufficiency
Management of Hyponatraemia?
Correct underlying cause
- Replace Na and water at the same rate they were lost. Beware if you replace too fast you get central pontine myelinolysis.
- Chronic: 10mM/d
- Acute: 1mM/hr.
Low to high, pons will die
High to low, brain will blow.
Normally <0.5mmol/hr.
Asymptomatic chronic hyponatraemia
- Fluid restrict
Symptomatic/acute hyponatremia/dehydrated
- Caution rehydration with 0.9% saline.
If hypervolaemic consider frusemide
Emergency: seizure, coma
- consider hypertonic saline. (1.8%).
What is SIADH?
Concentrated urine: Na >20mM, osmolality >500.
Hyponatraemia or plasma osmolality <275.
Absence of hypovolaemia, oedema, or diuretics.
Causes of SIADH?
Resp: SCLC, pneumonia, TB
CNS: meningoencephalitis, head injury, SAH
Endo: hypothyroidism
Drugs: cyclophosphamide, SSRI, CBZ
Management of SIADH?
Treat cause and fluid restrict
Vasopressin receptor antagonist
- Demeclocycline
- Vaptans
Hypernatraemia presentation?
Thirst Lethargy Weakness Irritability Confusion, fits, coma Signs of dehydration
In children can lead to cerebral shrinkage. Can be due to dehydration, profuse, low-sodium diarrhoea.
Manage w
Causes of hypovolaemic hypernatraemia
GI Loss: diarrhoea, vomiting
Renal loss: diuretics, osmotic diuresis
Skin: Sweating, burns
Causes of euvolaemic hypernatraemia?
Decreased fluid intake
DI
Fever
Causes of hypervolaemic hypernatraemia ?
- Hyperaldosteronism (Increased BP, decreased K, alkalosis)
- Hypertonic saline.
Investigation of Hypernatraemia?
Increased Na
Dilute Urine
Dx: Water deprivation test
Management of hypernatraemia
Treat cause.
Manage with slow infusion over 48 to reduce risk of cerebral oedema.
Desmopressin if cranial.
Symptoms of hypokalaemia?
Muscle weakness Hypotonia Hyporeflexia Cramps Tetany Palpitations Arrhythmia
NB: decreased potassium exacerbates digoxin toxicity
ECG findings of Hypokalaemia?
Results from delayed ventricular repolarisation
- Flattened /inverted T waves
- Prominent U waves (after T waves)
- ST depression
- Long PR interval
- Long QT interval.
Causes of hypokalaemia?
Alkalosis
Increased insulin
B-agonists
Increased excretion
- GI: vomiting, diarrhoea, rectal villous adenoma
- Renal: RTA (esp Type 2), Bartter syndrome
- Drugs: diuretics, steroids
- Endo: Conn’s syndrome , Cushing’s syndrome
Decreased input
- Inappropriate IV fluid management
Management of general hypokalaemia?
- 1mM K = 200-300mmol total deficit
- Don’t give K if oliguric
- Never give STAT fast bolus
Management of mild hypokalaemia?
K >2.5
- Oral K supplements
- > 80mmol/d.
Severe: K<2.5 and/or dangerous symptoms - IV KCL cautiously - 10mmol/h (20mmol/h max) - Give centrally (burning sensation peripherally) Max central conc: 60mM Max peripheral conc: 40mM
Mg replacement
- Pts are often Mg deplete too
- Until Mg is replaced the K will not return to normal levels despite K replacement
- Give empiric Mg Replacement.
Symptoms of hyperkalaemia?
Fast, irregular pulse
Palpitations
Chest pain
Weakness
SIgns of hyperkalaemia?
Tall tented T waves Flattened P waves Increased PR interval WIdened QRS Sine-wave pattern --> VF
Causes of Hyperkalaemia?
Artefact
- Haemolysis
- K2EDTA contamination from FBC bottles
- Leucocytosis, thrombocytosis
- Drip arm
Internal distribution
- Acidosis
- Decreased insulin
- Cell death/tissue trauma/burns
- Digoxin poisoning
- Suxamethonium
Decreased excretion - Oliguric renal fialure - Addison's - Drugs: ACEi, NSAIDs, K-sparing diuretics (spiro) Heparin (inhibition of aldosterone secretion)
Increased input
- Excessive K therapy
- Massive transfusion
Management of hyperkalaemia?
Non-urgent
- treat cause: review meds
- Polystyrene sulphonate resin: Binds K in the GIT and decreased K over days.
Emergency: Evidence of myocardial instability or K >6.5
- 10ml 10% calcium gluconate
- 100ml 20% glucose + 10u insulin (actrapid)
- Salbutamol 5mg nebuliser
- Haemofiltration
- Calcium resonium 15g PO or 30g PR.
How does PTH affect Ca and PO4?
Increased Ca
Decreased PO4
Ionised Ca –> PTH release.
Renal effect of PTH?
- Increased Ca
- Decreased PO4 resorption
Increased 1a-hydroxylation of 25-OH Vit D3 in kidney - Increased HCo3 excretion (may –> mild met acidosis)
Bone effects of PTH?
Increased osteoclast activity –> increased Ca, increased PO4.
Vitamin D and Calcitriol role?
Hepatic 25 hydroxylation -_> 25-OH Vit D3 (calcidiol)
Renal 1a-Hydroxylation in kidney –> 1,25 (OH)2 Vit D3
- Increased by increased PTH, decreased Ca, decreased PO4.
Gut effect of PTH?
- Increased Ca and increased PO4 absorption
- Inhibition of PTH release
Magnesium effect of PTH?
decreased Mg prevents PTH release
- May –> Decreased Ca.
Plasma binding 2.2-2.6mM for calcium?
50% Albumin bound (decreased albumin –> decreased Ca).
- Alkalosis –> decreased albumin protonation –> increased Ca binding -> Decreased free Ca.
Therefore prolonged tourniquet application –> increased albumin –> increased Ca.
What is the presentation of hypocalcemia?
Spasms (Carpopedal = Trousseau’s sign (inflate BP cuff) - Wrist flexion and fingers drawn in.
Anxious, irritable
Seizures
Muscle tone increased: colic, wheeze, dysphagia
Orientation impaired (confusion)
Dermatitis: atopic, exfoliative
Impetigo herpetiformis (decreased Ca + pustules )
Chovsteks, Cardiomyopathy (increased QTc –> TdP) - Tapping over parotid causes facial muscle to twitch.
Causes of hypocalacaemia?
Commonest cause is CRF.
- With increased PO4
CKD, hypoparathyroidism, decreased Mg, acute rhabdomyolysis.
- With normal or decreased Po4
Osteomalacia
Active pancreatitis
respiratory alkalosis
Management of hypocalcaemia?
Mild
- Ca 5mmol QDS PO
- Daily Ca levels
CKD
- Alfacalcidol (1-OH- Vit D3
Severe
- 10ml 10% Ca gluconate IV (2.25 mmol over 30 mins)
- repeat as necessary.
Hypercalcaemia presentation?
Stones, bones, moans, groans.
- May also have increased Bp (Check Ca in all with HTN)
- Decreased QT interval.
Causes of hypercalcaemia?
Most commonly malignancy or primary HPT.
Hypercalcaemia with increased PO4 and increased ALP?
Increased bone turnover?
- Bone mets (breast, lung, kidney, prostate, colon)
- Sarcoidosis
- Thyrotoxicosis (bone metabolism)
- Lithium
Hypercalcaemia with normal ALP, increased PO4?
Myeloma
Hypervitamonosis D
Sarcoidosis
Milk alkali syndrome
Hypercalcaemia with normal or decreased PO4?
primary or tertiary HPT
Familial benign hypercalciuria
Paraneoplastic: PTHrP (but decreased PTH)
Investigations of hypercalcaemia?
Increased PTH = primary or tertiary PTH
Decreased PTH = most likely Ca
FBC, protein electrophoresis, CXr, bone scan.
Management of hypercalcaemia?
rehydrate
- 1L 0.9% saline/4hrs
- Monitor pts hydration state
Frusemide
- Only start once pt is volume replete
- Calciuric + makes room for more fluids
Bisphosphonates
- Ca bisphosphonate can’t be resorbed by osteoclasts
- Only use in hypercalcaemia of malignancy
(Can obscure Diagnosis -> Ca decreased ,Po4 decreased and PTH increased)
- Takes 2-3 days to work with maximal effect.
- Pamidronate, Zoledronate (IV).
Give advise about good hydration (as long as no impairment)
- Reassure that a low calcium diet is not necessary.
- Advise person to avoid any drugs or supplements that could exacerbate.
- Encourage mobilisationation
- Advise them to report any hypercalcaemia
Osteoporosis types?
Decreased Bone mass
Primary: age related
Secondary: Drug or other conditions
Risk factors for osteoporosis?
Steroids Hyperthyroidism, HPT, HIV Alcohol and Cigarettes Thin (BMI <22) Testosterone low Early menopause Renal/liver failure Erosive/inflammation bone disease (RA, myeloma) Dietary Ca low/malabsorption
FRAX looks at
- history of glucocorticoid use
- RA
- Alcohol excess
- History of parental hip fracture
- low BMI
- current smoking
Presentation of osteoporosis?
Vertebral Crush fracture
NOF or other long bone fractures
Investigations for osteoporosis?
Bone profile, FBC, U+E
DEXA. Liver test, CRP, TFTs.
DEXA Scan results?
Indications
- Low-trauma #
- women >65yrs with one or more risk factor
- Before giving long-term steroids >3months)
- Parathyroid disorders, myeloma, HIV.
Interpretation of DEXA scan?
T: no of SDs away from youthful average
Z: no. of SD away from matched average.
T>-1 = normal
T -1 - -2.5 = osteopenia
T
Management of Osteoporosis?
- Decision to instigate pharmacological management is based upon age, RFs, and BMD
- FRAX can estimate 10yr #rish.
Conservative
- stop smoking, decreased ETOH
- Weight bearing or balancing exercise (tai Chi)
- Ca and vit D rich diet.
- Home-based fall-prevention program with visual assessment.
Primary and secondary prevention of fractures in osteoporosis?
Bisphosphonates: alendronate is 1st line
Zolendronic acid is IV and if you can’t tolerate oral.
Ca and Vit D supplements: e.g calcium D3, Forte.
Strontium ranelate: bisphosphonate alternative.
- Dual action bone agent. Promotes osteoblasts, inhibits osteoclasts. Only taken if no other treatment for osteoporosis. Can cause SJS.
Alternatives for secondary prevention of osteoporotic fractures?
If they cannot take alendronate because of age, T-score, number of risk factors (parental history of hip fracture, alcohol intake of 4 or more units per day, RA).
Raloxifen: SERM, decreased Breast Ca risk with HRT.
Terparetide: PTH analogue –> new bone formation
Rarely given: Denosumab: Anti-RANKL –> Decreased osteoclast activity.
Bisphosphonate SEs
- GI upset
- Oesophageal ulceration/erosion
- Diffuse musculoskeletal pain
- Osteonecrosis of the jaw.
What is osteomalacia?
Decreased bone mineral content
- Excess uncalcified osteoid and cartilage
RF
- Vegan, breast milk, malabsorption, CLD, CRD.
Presentation of osteomalacia?
children = Rickets
- Knock-kneed
- Bone pain
- Craniotabes-
- Osteochondral swelling; Rachitic rosary
- Harrison’s sulcus.
Osteomalacia: adults (after epiphyseal fusion)
- Bone pain and tenderness
- fractures (NOF)
- Proximal myopathy due to decreased PO4.
What are the causes of osteomalacia?
- Vit D deficiency: malabsorption, poor diet, decreased sunlight
- Renal osteodystrophy: decreased 1a hydroxylation
- Drugs: AEDs –> Increased hepatic Vit D metabolism.
- Vit D resistance
- Hepatic disease: malabsorption and decreased 25 hydroxylation
Malignancy: oncogenic hypophosphataemia
- increased fibroblast growth factor-23 – >hyperphosphatemia
What are the investigations for osteomalacia?
Decreased Ca Decreased PO4 Increased ALP Increased PTH Decreased 25-OH Vit D (unless resistance)
X-ray
= Loss of cortical bone
- Looser’s zones: pseudofractures
- Cupped metaphyses in Rickets.
Management of osteomalacia?
Dietary: Calcium D3 Forte
Malabsorption or hepatic disease
- Vit D2 PO (ergocalciferol)
- Parenteral calcitriol
Renal disease or Vit D resistance
- 1a-OH Vit D3 (alfacalcidol)
- Decreased 1-25(OH)2 Vit D3 (calcitriol)
Monitor Plasma Ca
What is Paget’s Disease?
Increased bone turnover – bone remodelling, enlargement + weakness.
Phases of Paget’s disease?
Osteolytic
Mixed Osteolytic-osteoblastic
Quiescent osteosclerotic stage
Presentation of Paget’s disease?
Asymptomatic in 70%
Predominantly affects the axial skeleton
- Pelvis, lumbar spine, skulls, femur, tibia
Bone pain
Patholgical fracture
Deformity
Head enlargemet
Complications of Paget’s disease?
- Nerve compression: deafness ,radiculopathy
- High output CCF
- Osteosarcoma (<1% after 10yrs)
Investigations of Pagets?
Very high ALP (ca and po4 normal)
Bone scan: hot spots
X-ray = Bone enlargement, sclerosis, patchy cortical thickening
- wedge-shaped lytic lesions,
Osteoporosis circumscripta - well defined lytic skull lesions.
Management of paget’s
Analgesia
Alendronate: Decreased pain and or deformity.
Osteoporosis biochem?
Everything normal
Osteomalacia biochem?
Ca low
PO4 low
ALP high
PTH high
Primary HPT cause?
Parathyroid adenoma or hyperplasia.
Hypercalcaemia
- Bloods =
High PTH, High Calcium, low PO4.High ALP.
Secondary HPT cause?
Chronic renal failure
Vit D deficiency
Malabsorption
Bloods
- High PTH, Low calcium, high PO4, high ALP
Tertiary HPT cause?
Parathyroid hyperplasia due to prolonged 2ndry HPT?
- High calcium, high PO4, high ALP, high PTH.
Characteristics of HPT?
Osteitis fibrosa cystica
- Subperiosteal erosions
- Acral osteolysis
- Cysts
- Brown tumours
- Pepperpot skull
Hypo PTH?
Low Ca, high PO4, normal ALP, Low PTH.
Renal osteodystrophy?
PO4 retention + low Vit D –> decreaseD Ca –> increased PTH.
Osteomalacia, osteosclerosis, osteoporosis.
Types of Hyperlipidaemia?
Common primary hyperlipidaemia
Familail primary hyperlipiaemia
2ndry hyperlipidaemia - increased LDL (nephrotic syndrome, hypothyroidism, Cushings) or mixed due to T2DM, ETOH.
Familial Primary Hyperlipidaemia
Primary hypercholesterolaemia
- ApoB (LDL receptor defect = increased LDL. AD disoder caused by a mutation in the gene coding the low-density lipoprotein LDL receptor. Causes early-onset hypercholesterolaemia.
FH = xanthelasma, tendon xanthoma, corneal arcus, raised cholesterol and LDL.
Combined hyperlipiaemia
- LDL increased + increased TG
Lipoprotein lipase deficiency
- Increased Chylomicrons
Presentation of hyperlipidaemia?
CVD, xanthomata (eruptive, tuberous at elbows, knees, planar - ornage streaks in palmer creases, xanthalesma: eyelids
Pancreatitis.
Management + Aims of hyperlipidaemia
Aim TC: <4
TC:HDL ratio <4.5
1st line
- Statins - Simvastatis 40mg PO node
- HMG-CoA
Can also use: Fibrates, PPARalpha antagonist
Ezetimibe: inhibits cholesterol absorption
Niacin/nicotinic acid: increased HDL, Decreased LDL.
Acute INtermittent Porphyria
GI pain, constipaiton, CV: increased HR, BP.
Neuropsych + red urine.
Precipitants = P450 inducer, stress, infection.
INcreased Urine PBG and ALA.
Manage with supportive anaglesia, IV fluids, carbohydrate.
Can give IV haematin.
Porphyria Cutanea Tarda
Commonest porphyria
Only cutaneous manifestation
- Photosensitivity: blistering skin lesions
- Facial hyperpigmentation
- Increased urine + se porphyrins
- Increased se ferritin
Avoid sun, phlebotomy/iron chelators.
Cholorquine.
Hyperlipidaemia secondary cause leading to a predominately hypertriglyceridemia?
DM (T1+2) Obesity Alcohol Chronic renal failure Drugs: thiazides, non-selective beta-blockers, unopposed oestrogen.
Hyperlipidaemia secondary cause leading to a predominately hypercholesterolaemia?
Nephrotic syndrome
Cholestasis
Hypothyroidism
Hypophophataemia
Can be caused by DKA
Phosphate 0.65-0.81 = Mild
0.32-0.65 = Moderate
<0.32 = Severe
Rise in insulin causes phosphate to shift into intracellular compartment.
Other causes:
- Alcohol excess
- Acute liver failure
- DKA
- refeeding syndrome
- Primary hyperparathyroidism
- Osteomalacia
Consequences
- red blood cell haemolysis
- White blood cell and platelet dysfunction
- Muscle weakness + rhabdo
- CNS dysfunciton.
Management
- Continue with current insulin therapy and initiate parenteral phosphate replacement.
Treatment of hyperuricaemia?
No treatment to prevent gout.
Gout is associated with high level of uric acid however it is possible to have hyperuricaemia without any noticeable effects.
Recommend against primary prevention of gout.
Hyperuricaemia?
Increased levels of uric acid may be seen secondary to either increased cell turnover or reduced renal excretion of uric acid. Hyperuricaemia may be found in asymptomatic patients who have not experienced attacks of gout
Hyperuricaemia may be associated with hyperlipidaemia and hypertension. It may also be seen in conjunction with the metabolic syndrome
Increased synthesis Lesch-Nyhan disease myeloproliferative disorders diet rich in purines exercise psoriasis cytotoxics
Decreased excretion drugs: low-dose aspirin, diuretics, pyrazinamide pre-eclampsia alcohol renal failure lead
ALP raised and raised calcium?
Bone mets
Hyperparathyroidism
ALP raised and low calcium
Osteomalacia
Renal failure
Causes of raised ALP?
liver: cholestasis, hepatitis, fatty liver, neoplasia
Paget’s
osteomalacia
bone metastases
hyperparathyroidism
renal failure
physiological: pregnancy, growing children, healing fractures
