Chemical Pathology Flashcards
Intracellular anions
Protein and Phosphate
Extracellular anions
Cl and HCO3
Formula for calculated plasma osmolarity
2(Na+K) + urea + glucose
Formula for osmolar gap
Measured osmolarity-calculated osmolarity
Anion gap formula
Na + K -Cl -HCO3
Causes hypernatremia
Insufficient intake
Water loss relative to Na loss: DI, osmotic diuresis, primary aldosteronism
Causes hypokalemia
Cellular uptake: insulin, alkalosis
Increased loss: D&V, fistulae, increased mineralocorts, diuretics, RTA 1 and 2
Causes hyperkalemia
Cellular loss: acidosis, severe hemolysis/rhabdomyolysis
Decreased loss: Renal failure, decreased mineralocorts (RTA 4), K+-sparing diuretics
Treatment hyperkalemia
Stabilize myocardium with 10mL 10% calcium gluconate
Drive K into cells: salbutamol, insulin +50mL 50% dextrose
Mop up K: calcium resonium, hemofiltration
Causes hypocalcemia
Absence parathyroids (parathyroidectomy, DiGeorge), Vit D defic, renal disease
Causes hypercalcemia
Primary hyperparathyroidism, myeloma, bony mets, PTHrp, granulomatous disease, vit D intoxication, diuretics, tertiary hyperparathyroidism, milk-alkali syndrome
Sxs hypercalcemia
Bones (osteitis fibrosa cystica), stones, moans (fatigue, confusion), and groans (vomiting, constipation, pain)
Normal GFR
60-120 mL/min
Causes of white cell casts in urine
Pyelonephritis
Causes of red cell casts in urine
Glomerulonephritis, severe tubular damage
Calcium oxalate stones
75%.
Radio-opaque.
Metabolic/idiopathic
Triple phosphate stones
17%
Radio-opaque
May form staghorn calciuli–PROTEUS MIRABILIS
Uric acid stones
5%
Radio-lucent
Hyperuricemia (gout, Lesch-Nyhan)
Cysteine stones
1%
Semi-opaque
Renal tubular defects, cystinuria
Gout
- Type crystals
- Presentation
- Tx for acute and chronic
M>F
Monosodium urate crystals: negatively birefringent
Exquisite pain
Red, hot, swollen joint
1st MTP or big toe (podagra) classic
NSAIDs for acute tx; allopurinol or chronic. Colchicine lowers urate levels
Pseudogout
Pyrophosphate crystals-positively birefringent
Self-limiting: 1-3 weeks
Dx-Cushings syndrome
Midnight plasma cortisol
Low dose DEXA test
Salivary cortisol
Urinary free cortisol
Conn’s syndrome
“Hyperfunction of aldosterone-secreting cells#. Increased aldosterone, decreased renin
Dx-Addison’s
Short synacthen test
When does CRP peak?
48 hrs
Function ceruloplasmin
Mops up superoxide radicals
Ferritin increased in which conditions
Fe overload
Acute inflammation
Test for B1 deficiency
RBC transketolase
Test for B2 deficiency
RBC glutathione reductase
Test for B6 deficiency
RBC AST activation
Reactive hypoglycemia/Post-prandial
Hypo following food intake Post-gastric bypass Hereditary fructose intolerance Early diabetes In insulin-sensitive individuals after exercise or large meal
Factitious hypoglycemia
Decreased glucose, increased insulin without increased C-peptide
Think of those with access to insulin…often nurses on exam questions
Sulfonylurea’s effect on glucose
Causes increased insulin production therefore lowers glucose
Essential amino acids
"PVT M.T. HILL" Phenylalanine Valine Threonin Methionine Tryptophan Histidine Isoleucine Leucine Lysine
Bariatric surgery procedures
Banding
Sleeve gastrectomy
Roux-en-Y (gold standard)
Marasmus
Caloric malnutrition
Severe muscle wasting, no s/c fat, growth retardation
Kwashiorkor
PROTEIN malnutrition Edematous Scaling/ulceration Lethargy Large liver, s/c fat
Anterior pituitary hormones
LH FSH GH ACTH TSH PRL
Posterior pituitary hormones
Stored only
Oxytocin
ADH
CPFT triple test
Hypoglycemia should increase CRF and thus ACTH, GHRH and GH
TRH stimulates TSH and PRL
LHRH stimulates LH and FSH
If pituitary failure, failure for GH, cortisol, LH, FSH to respond.
Urgently needs hydrocortisone
Also needs thyroxine, estrogen and GH replacement
Tx for PRLoma
Da agonist e.g. bromocriptine or cabergoline
Dx Acromegaly
OGTT
Glucose should decrease GH but stays high if acromeg
Renal osteodystrophy
All skeletal changes associated with chronic renal disease
- increased bone resorption (osteitis fibrosa cystica)
- Osteomalacia
- Osteosclerosis (can cause deafness or pain by pinching nerves)
- Growth retardation
- Osteoporosis
Buffers of H+
HCO3-/H2CO3
Hb-/HHb
HPO4-/H2PO4
Location in kidney where bicarb (HCO3) is reabsorbed
Proximal tubule
Causes metabolic acidosis
Increased H+ production (e.g. DKA) Decreased H+ excretion (e.g. renal tubular acidosis) Bicarb loss (e.g. intestinal fistula)
Causes metabolic acidosis with increased anion gap
MUD PILES Methanol Uremia DKA Propylene glycol Iron/INH Lactic acidosis Ethylene glycol Salicylates
Metabolic Alkalosis Causes
H+ loss (e.g. pyloric stenosis)
Hypokalemia (H+/K+ exchangers)
HCO3 ingestion
Normal serum concentration K+
3.5-5mmol/L
First ECG sign seen with hyperkalemia
Symmetrical peaked/tented T waves (“Eiffel Tower t waves)
ADH receptors
V2 in renal tubular cells (aquaporin channels)
V1 on vascular smooth muscle (vasoconstriction)
Tx hypokalemia
If 3-3.5: oral KCl (2 sando-K tablets tds for 48hrs)
If
Signs hypovolemia
tachycardia, postural hypotension, dry mucous membranes, reduced skin turgor, confusion/drowsiness, reduced urine output
Clinical signs hypervolemia
Increased JVP
Bibasal crackles
Peripheral edema
Causes hypovolemic hyponatremia
Diarrhea
Vomiting
Diuretics
Causes euvolemic hyponatremia
Hypothyroidism
Adrenal insufficiency
SIADH
Causes hypervolemic hyponatremia
Cardiac failure
Cirrhosis
Nephrotic syndrome
Causes SIADH
CNS pathology
Lung pathology
Drugs: SSRIs, TCAs, opiates, PPIs, carbamaz
Tumors
Dx-SIADH
No hypovolemia, hypothyroidism, adrenal insufficiency
Reduced plasma osmolality and increased urine osmolality
Na correction
Do not correct more than 12mmol/L in first 24 hours–risk central pontine myelinolysis
Central pontine myelinolysis
Quadriplegia, pseudobulbar palsy, seizures, coma, death
Tx-SIADH
Water restriction
Demeclocycline (decreases collecting tubule responsiveness to ADH)
Tolvaptan (V2 antag)
PTH-mechanism for increasing calcium
Kidneys: increases Ca reabsorption, upregulates 1-alpha-hydroxylase
Intestine: increases Ca absorption
Bone: increases bone resorption
Causes of high calcium and low PTH
Malignancy
Sarcoid
Thyrotoxicosis
Milk alkali syndrome
Causes of high calcium and high or inappropriately normal PTH
Primary hyperparathyroidism
Familial hypocalciuric hypercalcemia (rare)
Primary hyperparathyroidism
Parathyroid adenoma/hypoplasia/carcinoma
Associated with MEN I
Hypercalcemia in malignancy-causes
Humoral calcemia of malignancy (SCC lung secretes PTHrp)
Bone mets
Hematological malignancy (e.g. myeloma)
Hypocalcemia causes-NON PTH driven
Vit D deficiency CKD PTH resistance (pseudohypoparathyroidism)
Causes hypocalcemia due to low PTH
Surgical removal parathyroids
AI hypoparathyroidism
Congenital e.g. DiGeorge
Mg deficiency
T score in osteoporosis
T score in osteopenia
-1.5 to -2.5
Causes osteoporosis
Failure to attain peak bone mass
Early menopause
Bone loss during adulthood: lifestyle, endocrine (hyper-PRLemia, thyrotox, Cushings)
Steroids
Tx-osteoporosis
Lifestyle: stop smoking and drinking, weight bearing exercise
Drugs: Vit D/Ca, bisphosphonates, teriparatide, strontium, SERM (raloxifene)
Clinical features osteomalacia
Bone and muscle pain
Increased fracture risk
Low Ca and PO4, raised ALP
Looser’s zones (pseudofractures)
Clinical features rickets
Bowed legs
Costochondral swelling
Widened epiphysis at wrists
Myopathy
Paget’s disease
Disorder of bone remodeling
Focal pain, warmth, deformity, #, SC compression, malig, high output cardiac failure
Increased ALP
Tx with bisphosphonates
Renal osteodystrophy
Due to secondary hyperparathyroidism and retention of aluminum from dialysis fluid
Which two types renal stones are radiolucent?
Uric acid
Cysteine
Albumin
Maintains oncotic pressure, source of amino acids, acts as buffer, binds ligands
Decreased in acute inflamm response, liver failure, nephrotic syndrome
Alpha-1-antitrypsin
Degrades elastase
Deficiency causes tissue degradation (liver, lung)
haptoglobin
Mops up free Hb.
Thus decreased in intravascular hemolytic anemias
Ceruloplasmin
Carries copper
Decreased in Wilsons
Causes increased CSF
Trauma, infection (MENINGITIS), spinal block
Causes transudate effusions
Decrease in oncotic pressure:
CCF, liver failure, hypoalbuminemia, peritoneal dialysis
Causes exudate effusions
Malignancy PE RA/SLE TB Hemothorax
AFP as tumor marker
HCC
Testicular cancer
Tx-hypoglycemia
Alert and orientated: lucozade, sandwich
Drowsy/confused but swallow intact: buccal glucose
Unconsc or unsafe swallow: IV 50mL 50% gluc or 100mL 20% gluc
Causes hypoglycemia
Diabetes Fasting/reactive BOOZE Organ failure Insulinoma Post-gastric bypass Drugs Extreme weight loss Factitious
Neonatal hypoglycemia
Premature
Infant diabetic mother
IUGR/SGA
Inborn errors metabolism
Persistent neonatal hypoglycemia, raised FFA, normal ketones
FA oxidation defects
MCADD
GSD type 1 (von Gierke’s)
HMG CoA lysase deficiency
Inborn errors metabolism with heptaomegaly
Galactosemia
Fructose-1,6-phosphatase deficiency
GSD 1, 3, or 6
Prader-Willi
Maternal imprinting; paternal gene deleted/mutated.
Angelman Syndrome
Paternal imprinting; maternal gene deleted/mutated.
“Happy puppet syndrome”: inappropriate laughter, seizures, ataxia, severe intellectual disability
Hypophosphatemic rickets
X-dominant.
Increased PO4 wasting at proximal tubule
Mitochondrial myopathies
Rare
Myopathy, lactic acidosis, CNS disease.
Ragged red fibers
FAP
Mutation in APC gene on chromo 5
Hereditary hemorrhagic telangiectasia
Aka Osler-Weber-Rendu
Telangiectasias, recurrent epistaxis, skin discolorations, AVMs
NF1
Cafe-au-lait spots, cutaneous neurofibromas
NF2
Bilateral acoustic schwannomas, juvenile cataracts, meningioas, ependymomas
Tuberous Sclerosis
Multiorgan system involvement
Benign hamartomas
Lab findings in Duchennes
Increased CPK and aldolase
Myotonic type I dystrophy
CTG trinucleotide repeat in DMPK gene.
Myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmias
Dystrophin
Anchors muscle fibers, especially skeletal and cardiac (note that DCM is most common cause death in muscular dystrophy)
Loss of dystrophin causes myonecrosis
Tri-nucleotide repeat disorders
Huntingtons
Freidrich ataxia
Myotonic dystrophy
Fragile X
Down’s: quad screen
Decreased: AFP, estriol
Increased: inhibin A, hCG
Decreased PAPP-A
Downs
Edwards
Patau
Vit B complex deficiencies-typical symptoms
Dermatitis
Glossitis
Dementia
B1
Thiamine, a component of TPP
Thiamine pyrophosphate (TPP)
In pyruvate DH (links glycolysis to TCA cycle)
alpha-ketoglutarate DH (TCA cycle)
Transketolase (HMP shunt)
Branched chain ketoacid DH
Thiamine deficiency
Impaired glucose breakdown causing ATP depletion worsened by glucose infusion. Highly aerobic tissues (brain, heart) affected first.
Beriberi or Wernicke’s
Wet beriberi symptoms
High output HF (DCM), edema
Dry beriberi symptoms
Polyneuritis, symmetrical muscle wasting
B2
Riboflavin. Components of FAD, FMN–cofactors in redox reactions, e.g. succinate DH
B2 deficiency
Cheilosis, corneal vascularization
B3
Niacin. Part of NAD+, NADP+ (in redox rxns)
*Synth requires B2, B6
B3 deficiency
Glossitis. Pellagra when severe.
Pellagra symptoms
Diarrhea
Dermatitis
Dementia
Causes of pellagra
Hartnup disease (decreased tryptophan)
Malignant carcinoid syndrome
INH (decreases B6 which is required for B3 synth)
B5
Pantothenate. Part of CoA and fatty acid synthase
Deficinecy: dermatitis, enteritis, alopecia, adrenal insufficiency
B6
=Pyridoxine. Part of pyridoxal phosphate (cofactorin transamination e.g. ALT, AST), carbox reactions, glycogen phosphorylase
Synthesis of cystathionine, heme, niacin, histamine, NTs (5HT, E, NE, Da, GABA)
B6 deficiency
Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias (since no heme production)
B7
Biotin
Cofcator for carbox enzymes
Deficiency rare (dermatits, enteritis, alopecia)
B9
Folic acid
Converted to THF. Important for synth nitrogenous bases, e.g. in RNA, DNA
B9 deficiency
Macrocytic, megalobastic anemia, glossitis
Increased homocysteine, normal methylmalonic acid
Seen in alcoholism, pregnancy, drugs (phenytoin, sulfonamides, MTX)
B12
Cobalamin
Cofactor for homocyteine methyltransferase, methylmalonyl CoA
B12 deficiency
Caused by strict veganism, malabsorption (sprue, enteritis, Diphyllobothrium latum–fish tapeworm), lack intrinsic factor (pernicious anemia, gastric bypass), absnece terminal ileum (Crohn’s)
Vit C
Fe3+ –> Fe2+
Hydroxylation proline, lysine
In beta hydroxylase (converts Da to NE)
D3
Cholecalciferol
Milk, sun
D2
Ergocalciferol
Plants
Vit E
Protects RBC from free radical damage
Vit E deficiency
Hemolytic anemias
Acanthocytosis
Muscle weakness
Posterior column and spinocerebellar tract demyelination
Essential fructosuria
AR defect in fructokinase
Fructose in urine and blood
Asymptomatic and benign
Fructose intolerance
AR. Deficiency aldolase B
Fructose-1-P accumulates and decreases PO4 which halts glycogenolysis and gluconeogenesis
Symptoms following ingestion fruit, juice, or honey
Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
Galactokinase deficiency
Deficiency galactokinase
AR
Galacitol accumulates
Sxs: galactose in blood, urine. Infantile cataracts. May initially present as failure to track objects or develop social smile
Classic galactosemia
AR deficiency galactose-1-P-uridyltransferase
Sxs: FTT, jaundice, hepatomegaly, infantile cataracts, intellectual disability
Cystinuria
AR defect renal tubular transporters for cysteine, ornithine, lysine, arginine (COLA).
XS cystine in urine can precipitate cystine stones.
Tx: urinary alkalinization (K citrate, acetazolamide)
Homocystinuria
AR defects often affecting cystathionine synthase.
XS homocysteine.
Intell disability, osteoporosis, tall stature, lens subluxation, thrombosis, atherosclerosis
Type I glycogen storage disease
Von Gierke’s
AR. Deficient glucose-6-phosphatase.
Loads glycogen in liver (hepatomegaly), increased blood lactate
Type II glycogen storage disease
Pompe’s,
AR deficiency in lysosomal-alpha-1,4-glucosidase (acid maltase)
HEART (cardiomyopathy), liver, muscle.
Type III glycogen storage disease
Cori disease.
No debranching enzyme (alpha-1,6-glucosidase)
Milder version of von Gierke’s but no increase in lactate
Type V glycogen storage disease
McArdle’s
Increased glycogen in muscle–can’t break down due to lack skeletal muscle glycogen phosphorylase (myophosphorylase)
Also have painful muscle cramps, myoglobinuira after intense exercise, arrhythmias
Purines
Adenosine
Guanosine
Inosine
Urate
Final product of purine breakdown
Circulates in blood at level close to its solubility
Renal urate handling
90% reabsorbed
10% excreted
Rate limiting step (and enzyne) in de novo purine synthesis
PRPP to 5-phhosphoribosyl-1 amine
Enzyne: phosphoribosylamidotransferase, with ppat
Salvage pathway purine synthesis
Faster method
Hypoxanthine converted (via HGPRT) to INP Guanine converted (via HGPRT) to GNP
Lesch Nyhan
Deficiency in HGPRT (“He’s Got Purine Recovery Trouble”)
Devel delay by 6/12
Choreiform movements (basal ganglia)
Spasticity
Self-mutilation (85%), esp lip and finger biting
Hyperuricemia/gout
X linked
Causes increased urate production (primary)
Lesch-Nyhan Partial HGRPT deficiency Glycogen storage diseases Fructose intolerance PRPP synthetase overactivity
Causes increased urate production (secondary)
Myeloproliferative disorders
Lymphoproliferative disorders
Chronic hemolytic anemia
Severe psoriasis
Causes decreased urate excretion
CKD
Down’s syndrome
Pb poisoning
Aspirin
Gout
Monosodium urate crystals
Negatively birefringent crystals (yellow when parallel, blue when perpendicular)
Pseudogout
Calcium pyrophosphate crystals Positively birefringent (blue when parallel, yellow when perpendicular)
Acute gout
Exquisite pain
Affected joint is hot, swollen, tender
1st MTP joint is first site in 50%–involved in 90% overall
Tx with NSAIDs, colchicine, glucocorticoids
Chronic gout (tophaceous)
Not that painful
Allopurinol
Drink plenty water
Slow down on the vodka
Probenecid
Schmidt’s syndrome
Addison’s disease AND primary hypothyroidism
Test for Addison’s
Short synacthen test
Cholesterol transport in fasting plasma
VLDL: 13%
LDL: 70%
HDL: 17%
Dyslipidemia
Hypercholesterolemia
Hypertriglyceridemia
Mixed hypolipidemia
Hypolipidemia
Primary hypercholesterolemia type II
AD mutation LDL receptor, apoB, or PCSK9 genes.
Polygenic hypercholesterolemia
Multiple loci incl NP1L1, HMGCR, CYPA1 polymorphisms
Familial hyperaalphalipoproteinemia
Some cases associated with CETP deficiency
Phytosterolemia
Mutations ABC G5 and G8 (genes that prevent absorption plant sterols…atherosclerosis occurs earlier when mutations are present)
PCSK9
Bind LDL receptor and promote its degradation
Gain-of-fn mutations can cause familial hypercholesterolemia
Loss-of-fn mutations associated with low LDL levels
Primary hypertriglyceridemia, Familial type I
Lipoprotein lipase or apoC II deficiency
Primary hypertriglyceridemia, Familial type IV
Increased synthesis TG
Primary hypertriglyceridemia, Familial type V
Sometimes due to apoA V deficiency
CVD risk with lipid levels
Inversely related to HDL levels; directly related to LDL levels
Statins
Best at decreasing LDL. Slight decrease in TGs and slight increase in HDL
Nicotinic acid
Can’t really get this any more
Fibrates, e.g. gemfibrozil
Not very good at decreasing LDL
Very good at decreasing TGs and decent at increasing HDL
Ezetimibe
Blocks cholesterol absorption
Decrease in LDL levels
Cholestyramine
Bile acid binding resin
Decrease in LDL
Orlistat
Inhibits pancreatic lipase
Steatorrhea
Difference between serum osmolality and serum osmolarity
Osmolality: mOsm/kg
Osmolarity: mOsm/L
Often incorrectly used in medical literature.
By the bedside addition of Na, K etc is osmolarity.
Lab tends to use osmolality.
However, there are complex equations to convert between two
Controls uptake of iodide into thyroid
TSH
Blocks uptake of iodide into thyroid
Perchlorate
Thionamides
Block iodination of tyrosine residues
E.g. carbimazole, propylthiouracil
Thyroid peroxidase
Converts iodide into iodine
Thyroglobulin
Converts iodine to thyroxine
Active thyroid hormone
T3
Drugs that can cause hypothyroidism
Amiodarone
Lithium
Subclinical hypothyroidism
Compensated.
Increased TSH, normal T4
Associated with hypercholesterolemia
Pregnancy’s affect on thyroid
hCG resembles TSH so can become hyperthyroid
NORMALLY, TSH decreases slightly and T4 increases, but with increased TGB, therefore euthyroid
Sick euthyroid
Alteration in pituitary-thyroid axis in non-thyroidal illness Can be any severe illness. Low T4 when severe, High normal TSH, later decreased Low T3 and reduced T3 action
Causes hyperthyroidism
Graves (40-60%)
Toxic multinodular goiter (30-50%)
Single toxic adenoma (5%)
High uptake on technetium scan
Graves
Toxic multinodular goiter
Single toxic adenoma
Low uptake on technetium scan
Subacute thyroiditis
Post-partum thyroiditis
Papillary thyroid carcinoma
Most common type of thyroid cancer (80%)
RFs: exposure to ionizing radiation in childhood
Orphan Annie nuclei, psammoma bodies
Great prognosis
Follicular thyroid carcinoma
Surrounded by fibrous capsule
Mets hematogenously spread (NB most carcinomas spread via lymphatics; this one is an exception)
Must differentiate from follicular adenoma (spread through capsule)
Medullary thyroid carcinoma
Prolif parafollicular C cells (thus, may get increased calcitonin thus hypocalcemia)
5% thyroid carcinomas
Familial causes due to MEN syndrome (MEN 2A and 2B). Note both MEN 2A and 2B associated with RET oncogene
Anaplastic carcinoma
Rock hard thyroid + elderly
Often invades local structures, causing dysphagia or resp compromise
Poor prognosis
Subacute (de Quervain’s) thyroiditis
Follows viral infection
Tender thyroid with transient hyperthyroidism
Self-limiting. 15% may progress to hypothyroidism
Riedel fibrosing thyroiditis
Chronic inflamm with extensive fibrosis of thyroid
Presents as hypothyroidism with “hard as wood” nontender thyroid
Clinically mimics anaplastic carcinoma, but pts younger (40s) and no malignant cells
Hashimotos
AI destruction thyroids
HLA-DR5
MCC hypothyroidism in areas where iodine sufficient
Initially may present as hyperthyroidism (follicles damaged)
Anti-thyroglobulin and antithyroid antibodies
Increased risk B-cell (marginal zone) lymphoma
Multinodular goiter
Enlarged thyroid with multiple nodules
Relative iodine deficiency
Usually non-toxic (euthyroid)
Rarely, can have regions that become TSH-independent….toxic goiter
Cretinism
Hypothyroidism in neonates and infants
Mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, umbilical hernia.
Causes: Maternal hypothyroidism in early pregnancy Thyroid agenesis Dyshormonogenic goiter Iodine deficiency
Guthrie test (heell prick)
The actual definition of myxedema
Accumulation of glycosaminoglycans in skin and soft tissue. Results in deepening of voice and large tongue
Seen in hypothyroidism, pretibial myxedema in hyperthyroidism
Common problems in low birth weight babies
RDS Retinopathy of prematurity Interventricular hemorrhage PDA Necrotizing enterocolitis
Nephron embryology (basics)
Nephrons start developing from week 6
Start producing urine from week 10
Functional maturity GFR not reached until about 2 years age
Why are young kids’ kidneys less able to compensate for problems?
Lower reabsorption capabilities (shorter prox tubule)
Slow excretion solute load
Limited amt Na available for H+ exchange
Reduced concentrating ability
Distal tubule relatively unresponsive to aldosterone
Hyponatremia in young children
Rare CAH (21 hydroxylase deficiency)
Causes prolonged neonatal jaundice
Prenatal infection/sepsis/hepatitis Hypothyroidism Breast milk jaundice hemolytic disease G6PD defic Crigler-Najjar Biliary atresia, choledoeal cyst
Toxicology
Analyzing samples for drugs/poisons and interpreting the significance
Forensics
Reports/results used in court
Coroner’s toxicology
(Section 3 Coroner's Act) Report following deaths to coroner: 1. Violent 2. Unnatural or sudden 3. Cause of death unknown
How does cocaine kill you?
Arrhythmias, acute HF, MI, coronary vasospasm
How do amphetamines kill you?
Direct toxic effect on the heart
Also cause hyperthermia, which causes rhabdomyolysis, which causes renal failure
Hair for toxicology reports
Blood/serum-drugs typically can’t be detected past 12 hrs
Drugs incorporated into hair from blood stream during growth phase
Hair grows about 1cm/mo = tape-recording of drug use
Use gas-chromatography/mass spec
Porphyria
Problem in heme synthesis
Often get funny colored urine and cutaneous symptoms
Acute porphyrias
AIP
Hereditary coproporphyria
Variegate porphyria
All AD
Only AIP does not have skin lesions
Acute Intermittent Porphyria (AIP)
Defective HMB synthase (PBG deaminase)
Abdo pain and vomiting, tachycardia, HTN, seizures, psychosis
Hereditary coprophyria
Defective coporphyrinogen oxidase
AD
Skin lesions
Variegate porphyria
Defective protoporphyrinogen oxidase
AD
Skin lesions
Non-acute porphyrias
Porphyria cutanea tarda (PCT)
Erythropoietic protoporphyria
Congenital erythropoietic porphyria
Porphyria cutanea tarda
Defective uroporpyrinogen decarboxylase
Skin lesions after sun exposure
Erythropoietc protoporphyria
Defective ferrochelatase
Skin lesions after sun exposure
Congenital erythropoietic porphyria
Defective uroporphyrinogen III synthase
Skin lesions after sun exposure
