Flashcards
Pathology- Biochemistry 2
Cards in this deck (52)
- 1What is renal 1 alpha hydroxylase stimulated by?-low plasma phosphate
-increased PTH
-oestrogens, PRL, GH - 2Where is calcitonin produced and what are its physiological effects? What is its clinical use-Produced in the parafollicular C cells of the thyroid
- secreted in response to an increase in ionised calcium
1) bone - inhibits osteoclasts activity therefore reduces bone resorption
2) kidney - reduced tubular reabsorption of Ca and PO4
Net effect: decreased Ca2+ and PO4
Uses - tumour marker in thyroid cancer
-therapeutic treatment of hypercalcaemia and pagets diseae - 3What are the ECG changes seen in hypercalcaemia?-Shortened QT
-bradycardia - 4What are the artefactual causes of hypercalcaemia?-dehydration
-prolonged use of a tourniquet - 5Aetiology of primary hyperparathyroidism-85% single adenoma
-10% hyperplasia
1-3% carcinoma - 6What is humoral hypercalcaemia of malignancy?Release of bone resorptive factors by the tumour eg
-PTHrp by bronchial carcinoma
-TNF
-IL-1 - 7What are the renal causes for hypercalcaemia?-thiazide diuretics
-familial hypocalciuric hypercalcaemia - 8Signs and symptoms of hypocalcaemia1) neurological - lethargy, depression, psychosis
-tetany, paraesthesia, cramps
2) CV - prolonged QT
-arrythmias
3) soft tissue - cataracts
-brittle nails/hair - 9Artefactual causes of hypocalcaemia-reduced plasma albumin (lower total calcium) (measure adjusted)
-unsuitable sample - 10Causes of hypocalcaemia secondary to decreased flux from bone1) PTH deficiency - surgical
-di george syndrome
-idiopathic
-infiltrative
2) PTH resistance - magnesium resistance
-pseudohypoparathyroidism
3) treatment with anti resorptives eg bisphosphonates - 11Causes of hypocalcaemia1) artefactual (other slide)
2) decreased Vit D intake/absorption - dietary, coeliac, renal 1 alpha hydroxylase deficiency,
3) decreased flux of calcium from bone
4) increased flux of calcium to bone eg hungry bone syndrome
5) extraskeletal sequestration by acute pancreatitis - 12Cardiac markers in MI-troponin
-CKMB
-myoglobin
-fatty acid binding protein
-copeptin - 13What are the three troponin subunits?1) Troponin T - tropomyosin binding subunit
2) troponin I - myosin ATPase inhibiting subunit
3) troponin C - calcium binding subunit - 14Which troponins are specific to the heart and what are the other causes of raised troponins?-T and I
Other causes: - CCF
-renal failure
-sepsis
-AF
-myocarditis
-rhabdomyolysis
-PE
-Electrical burns - 15Use of myoglobin, CKMB and FABP as cardiac markers1) myoglobin - Rises and falls rapidly
-not cardiac specific
-good for rule out
-not used in hospitals mainly for research purposes
2) CKMB - produced in serum, muscle, heart and brain
-useful in reinfarction
-used in conjunction with troponin
3)FABP - protein in myocardial lipid synthesis
-found in heart, kidney, muscle
-sensitive but not specific - 16When is BNP produced and what is its effect? What prognostic value does it have?-secreted by the ventricles in response to tension
-BNP binds and activates receptors causing reduction in systemic vascular resistance, central venous pressure and natriuresis
-Prognostic indicator of death, heart failure, risk prediction of MI recurrence
-can be used to diagnose and grade severity in CCF - 17Causes of secondary hypertension-renovascular disease
-renal parenchyma disease
-cushings
-conns syndrome
-hyperparathyroid (Ca2+ deposits in the vessels)
-acromegaly
-phaeochromocytoma
-hyperthyroid - 18Diagnosis of phaeochromocytoma and limitations1) 24 hours urine to look for urine catecholamines and metanephrines.
-good sensitivity and specificity
-affected by medications including paracetamol, cough syrups, TCAs, beta blockers
-samples need to be collected in acid (not stable outside of body
2) plasma metanephrines - high sensitivity but low specificty
-patient must rest for 15-30 mins
-affected by caffeine alcohol smoking
- - 19Cause of secondary hyperaldosteronism-Increased activity of RAAS
-renin producing tumour
-renal artery stenosis - 20What investigation is used in hyperaldosteronism and the results?-Plasma aldosterone to renin activity ratio
1) conns syndrome - high plasma aldosterone and low renin (suppressed)
2) secondary hyperaldosteronism - High renin and high aldosterone - 21What considerations must be taken in a plasma aldosterone renin activity ratio?-patient must be rested for 30 mins
-must not be on diuretics or ACE inhibitors or spironolactone - 22Pathogenesis of phenylketonuria-Mutation in the phenylalanine hydoxylase gene
-leads to absent or reduced enzyme activity or impaired binding of its cofactor BH4
-leads to a build up of phenylalanine and reduced tyrosine
-phenylalanine is neurotoxic and tyrosine is required for neurotransmitter synthesis (double whammy) - 23What are the three main categories of inherited metabolic disorders?1) disorders involving complex molecules
2) intoxication
3) energy insufficiency - 24Give a typical presentation of a patient with an IMD of complex molecules and give examples-symptoms are permanent, progressive, independent to intercurrent illness and unrelated to food intake
-involves cellular organelles and includes diseases that disturb the synthesis or catabolism of complex molecules
Examples: Lysosomal storage disorders
-peroxisomal disorders: x linked ALD, zellweggers
-congenital disorders of glycosylation
-cholesterol biosynthesis disorders eg smith optiz syndrome - 25Give a typical presenation of a lysosomal storage disorder-developmental and behavioural problems eg aggression
-macrocephaly
-coarse facial features
-kyphosis
-hepatosplenomegaly
-claw hands
-umbilical hernia - 26Examples of treatment options in lysosomal storage disorders-supportive/palliative care
-enzyme replacement therapy
-BM transplant
-substrate reduction therapy
Chaperone and gene therapy in research phase - 27Give a typical presentation of an IMD of intoxication-symptoms due to acute or progressive intoxication from the accumulation of toxic compounds proximal to the metabolic block
-presentation can be acute eg vomiting, lethargy, coma, liver failure
or can be chronic eg progressive developmental delay, cardiomyopathy - 28Give examples of IMD of intoxication-urea cycle defects
- 29Signs and symptoms of hyperammonaemiaacute tachypnoea, lethargy, vomiting convulsions, encephalopathy
- 30Causes of hyperammonaemia1) artefactual - delayed analysis, haemolysis, struggling infant
2) non metabolic - hepatic failure
-UTI (urease producing bacteria)
-TPN
-hypovolaemic shock
3) Inherited defects of the urea cycle
4) other inherited metabolic diseases - 31What is the commonest inherited defect of the urea cycle?Ornithine transcarbamylase deficiency
- 32What are the common symptoms of an IMD of impaired energy metabolism-hypoglycaemia
-hyperlacticacidaemia
-hypotonia
-myopathy
-cardiomyopathy
-SUDI - 33What is MCADD and how does it present? How is it managed-Medium chain acyl coA dehydrogenase deficiency
-presents with metabolic criss precipitated by fasting, illness, operations
Acute management - high dose IV glucose
-IV carnitine
Chronic - avoid fasting
-low fat high carb diet
- - 34Which conditions are now screened for in the NHS england newborn blood spot screening programme?9 disorders
-PKU
-maple syrup urine diseae
-homocystinuria
-MCADD
-isovalericaciduria
-glutaric aciduria type 1
-sickle cell
-CF
-congenital hypothyroidism - 35What is the henderson hasselbalch equation?pH=pKa + log[A-]/[HA]
- 36In which organs is ALP made?Major forms of ALP are in bone and liver. Placenta is also a major source especially during the third trimester. Gut may also produce ALP but to a lesser extent
- 37LFTs in cholestatic diseasePredominantly an ALP rise
- 38LFTs ih hepatocellular diseasePredominantly ALT rise
- 39Overview of bilirubin metabolism-haemoglobin and other haem compounds get broken down in RE system (especially spleen) to form bilirubin
-Bilirubin is carried by albumin to the liver
-bilirubin is conjugated to form bilirubin glucoronide
-conjugated bile is then exported via the bile duct and converted to urobilinogen, urobilins and finally stercobilins by bacteria in large intestine
-some urobilinogen is reabsorbed via the enterohepatic circulation and excreted in the urine as urobilin - 40Describe the main differences beween conjugated and unconjugated bilirubin1) unconjugated - insoluble in water
-no bilirubin in urine
-pre hepatic or hepatic
2) conjugated - soluble in water
-bilurin in urine
-hepatic or post hepatic - 41When is measuring GGT clinically useful?GGT is specific to the liver but not specific for particular forms of liver disease. May be used to differentiated between liver and bone disease when the ALP is raised but other LFTs are normal.
- 42What is Gilbert's syndrome and what are the biochemical findings?-Defect in the coagulation of bilirubin (deficiency of glucuronyl transferase)
-Isolated raised unconjugated bilirubin.
-enzymes normal - 43LFT in neonatal jaundice-increased unconjugated (breastmilk jaundice)
-Enzymes are age specific - 44LFTs in spherocytosis-increased unconjugated bilirubin with normal enzymes
- 45LFTs in cholangiocarcinomaqIncreased Conjugated bilirubin with deranged ALP
- 46LFT is Ca head of pancreasIncreased Conjugated bilirubin with deranged ALP
- 47LFT in acute hepatitisIncreased Conjugated bilirubin with deranged ALT
- 48LFT in pregnancyRaised ALP with normal bilirubin
- 49LFTs seen in alcohol abuse-Normal bilirubin
-May be deranged ALT or AST:ALT ratio
-GGT raised - 50What is hunters syndrome and which enzyme is deficient?-mucopolysaccharidoses type II.
-Defect in iduronate 2 sulfatase - 51Describe the hyponatraemia flowchart1) is it a pseudohyponatraemia?
2) is it a compensatory hyponatraemia?
3a) are they volume deplete? Renal loss - addisons, diureitcs. Urinary sodium >30 Extra renal loss - vomiting, diarrhoea. Urinary sodium <30
b) are they euvolaemic? SIAD or Hypothyroid. Urinary sodium >30
C) are they fluid overloaded? CCF, kidney failure, liver failure. Urinary sodium <30. - 52Use of a high dose dexmethasone suppression testGenerally, cushings disease will suppress but ectopic and adrenal causes will not
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- Flashcards on Pathology- Biochemistry 2, created by Harry Robertson on 04/04/2018.
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