Chemical Pathology Flashcards
How does estrogen appear in serum
Estradiol (ovaries) and estrone (from androstenedione in adipose)
60% albumin bound
38% SHBG
2% free (biologically active)
What favors Wolffian duct formation
Anti-Mullerian hormone
Testosterone
Define menopause
Permanent cessation of menstruation from loss of ovarian follicular fx for more than 12 months
Post menopausal woman are at more risk for…
CHD, osteoporosis
Causes of amenorrhea
Outflow tract/uterus disorders (duct problems, androgen insensitivity, Asherman's) Ovarian disorders (Turner's, premature ovarian failure) Pituitary disorders (prolactin secreting tumour, granulomatous infiltration, Sheehan's) CNS disorders (Kallman's, craniopharyngioma, weight loss, stress, exercise)
Define hirsutism
Male pattern hair growth with hyperandrogenism often associated with menstrual irregularity
Why testosterone high in PCOS
Elevated androgens and insulin suppress hepatic SHBG synthesis = more free testosterone
Features of PCOS
Menstrual irregularities Hyperandrogenism (hirsutism, acne, balding) Obesity (50%) Insulin resistance Multiple follicles
Hormones in adrenal medulla are complexed to …
Proteins (chromogranins)
What analyte is measured in neuroblastoma (product of dopamine degradation)
Homovanillic acid
What regulates (nor)adrenalin release
Chronic - cortisol
Acute - acetylcholine causing Ca influx
Where is adrenalin synthesized
Chromaffin cell (adrenal medulla)
Most common cause of congenital adrenal hyperplasia
21-hydroxylase deficiency
Three forms of congenital adrenal hyperplasia
Simple virilising form
Severe salt losing form
Non-classical form (very mild -> ?infertility)
Define Addison’s disease
Primary adrenal hypofunction
Impaired ability to secrete cortisol and aldosterone
Key features of Addison’s
Orthostatic hypotension
Low Na
High K
Test for Addison’s
Na, K, blood gas, renal functions Baseline cortisol ACTH levels (high in 1ry)
ACTH stimulation test (Synacthen test)
If Addison’s then poor cortisol response
What hormone can cause hyper pigmentation
ACTH
What drug can be used to treat pituitary tumour
Bromocrptine
Define gout
Recurrent inflammatory arthritis caused by deposition of monosodium urate crystals in synovial fluid
Pathogenesis of gout
Hyperuricaemia -> crystal deposition -> macrophage phagocytosis -> inflammatory cascade.
Causes of hyperuricaemia
Overproduction - enzyme defect, drugs(ethanol), obesity, malignancy, haemolytic disorders, myeloproliferative disorders.
Underexcretion - 1ry gout, diuretics, hypothyroid, hyperparathyroid, keto/lactic acidosis, renal insufficiency
Over consumption - meats, seafood, beer
Deficiency of hypoxanthine-guanine phosphoribosyltransferase
Lesch-Nyan syndrome
Prevention of gout
Decrease weight, alcohol, purine intake
Drugs - xanthine oxidase inhibitors (allopurinol), increase excretion (probenecid), increase uric acid metabolism (rasburicase)
Four characteristics of tumour lysis syndrome
Hyper - kalaemia, uricaemia, phosphataemia
Hypo - calaemia
Complications of hyperkalaemia
ECG changes
Cardiac arrhythmias
Vfib
Complications of hyperuricaemia
Acute renal failure
Kidney stones
Acute gout
Calcium decrease in tumour lysis due to
Binds proteins released by cells
Precipitates with phosphate
Long term: phosphate inhibits vitD activation
Complications of hypercalceamia
Cramps (tetany)
Convulsions
Cardiac arrhythmias
Prevention of tumour lysis
IV hydration
Urine alkalinisation
Hypouricaemic agents (eg allopurinol, rasburicase)
Treatment of tumour lysis syndrome
Kayexalate (decrease potassium)
Calcium replacement
Phosphate binders
DIALYSIS
Define multiple myeloma
Malignancy of a single clone of plasma cells
Causes of increased paraproteins
Myeloma/malignancy
Connective tissue disease
Primary amyloidosis
Benign conditions
Light Ig chains found in urine
Bence-Jones proteins
Clinical features of multiple myeloma
Bone infiltration = hypercalceamia, anaemia, osteolytic bone lesions, infection, bleeding.
Monoclonal proteins = elevated ESR, peripheral neuropathy, kidney failure, hyperviscosity syndrome
Investigations for multiple myeloma
Protein electrophoresis
Immunotyping
Bence-Jones proteins
Free light chain ratio
Causes of renal failure in multiple myeloma
Hypercalceamia - renal calcification
Hyperuricaemia
Light chain proximal tubal damage
Counter regulatory hormones in glucose control
Glucagon
Adrenalin
Cortisol
Growth hormone
Insulin causes
Glucose into cell (GLUT4)
Glycogen synthesis (inc glycogen synthase)
Protein synthesis
Fat synthesis/storage (inc Acetyl CoA carboxylate / lipoprotein lipase
Counters effects of counterreg hormones
Mechanism of insulin release
Glucose binds GLUT 2 on pancreatic Bcells. Causes increase in ATP which causes reduced efflux of K leading to depolarization and influx of Ca. Ca influx causes insulin release.
Define type 1 diabetes
B-cell destruction leading to absolute insulin deficiency
Subcutaneous nodule found in hyperuricaemia
Tophus
Define HbA1c
Non-enzymatic covalent glycation of the N-terminal valine on the beta chain of hemoglobin. Indications glucose level over RBC lifetime (120 days)
Shortfalls of HbA1c
Increased RBC lifespan - iron deficiency, pregnancy, splenectomy, aplastic crisis
Decreased RBC lifespan - haemolytic disease, sickle cell trait, pregnancy, chronic blood loss.
Haemoglobinopathies
Pathogenesis of DKA
No insulin.
Increase gluconeogenesis and glycogenolysis = hyperglycemia -> osmotic diuresis = dehydration.
Increased lipolysis = increased ketones = acidosis -> vomiting = dehydration
Diagnosis of DKA
Low pH
High glucose
High ketone
Pathogenesis of HONK
Low insulin.
Increased gluconeogenesis and glycogenolysis = hyperglycemia -> osmotic diuresis = dehydration. Increased blood viscosity = thrombosis. Increased plasma osmolarity = cerebral dehydration
Diagnosis of HONK
Very high glucose >33
High osmolarity >320
N/decreased pH
NO KETONES
What happens to K levels in DKA
K leaves cells in ketoacidosis (protein, glycolytic intermediates depleted and accumulating H displace K)
Excess intercellular K excreted by kidney.
Therefore, normal serum K despite profound decrease in intracellular K
Treatment of DKA
Rehydrate (avoid cerebral oedema)
Monitor/replace intracellular ions
Administer insulin until normal pH
Treat predisposing cause eg infection
Management of diabetes
Diet Exercise Manage complications Oral hypoglycemic drugs Insulin
Causes of hypoglycemia
LENDS Liver disease Endocrine disease (Addison's, GH def) Neoplasms (insulinoma) Drugs (insulin, alcohol) Sepsis
Define hypoglycemia
Glucose < 2.2 (<4.0 in diabetes)
Anxiety, weakness, faintness, headaches
Palpitations, tachycardia, sweating
What tubes needed when measuring glucose + why
Sodium fluoride = inhibits metabolism
Where are each of these found GLUT 1 GLUT 2 GLUT 3 GLUT 4
RBC, brain
Liver, pancreatic Bcells
Neurons, placenta, brain
Muscle and adipose tissue
Hormones that decrease appetite
GLP 1 Oxymodulin PYY Insulin Leptin
Hormone that increases appetite
Ghrelin
Thyroid function tests
TSH (screening test) Free T4 (monitor Rx in known disease) Free T3 (rarely tested - nonthyroidal illness, drugs, T3 toxicosis)
Other thyroid tests
Thyroglobulin (thyroid cancer)
Calcitonin (medullary thyroid canc)
Thyroid Abs
Causes of hyperthyroidism
Grave’s disease
Multinodular goitre
Toxic adenoma
Pituitary tumour
Causes of hypothyroidism
Autoimmune (Hashimoto’s and atrophic thyroiditis)
Iatrogenic
Iodine deficiency
2ndry hypothyroidism
Criteria needed to diagnose diabetes
Random blood glucose >11
Fasting glucose >7
OGT >11after 2 hours
HbA1c normal range
4-6%
Causes of microalbuminuria
Early diabetic nephropathy
Hypertension
In cervical cancer what can cause anaemia?
Blood loss
Lack of erythropoietin from post renal failure
Anaemia of chronic disorders
What compound does dipstix measure wrt ketones
Acetoacetate
Options for lowering potassium and mechanisms
Kayexalate - cation binding resin
Loop diuretics + fluid = renal K loss
Glucose + insulin = glycolysis etc
Reasons for urea increase but not creatinine
Pre renal failure
Accelerated protein catabolism
Why LDH increased in leukaemia
Tumour derives energy from anaerobic glycolysis. Therefore glycolytic enzymes found in plasma
Non malignant causes of isolated LDH increase
Haemolysis
Metaloblastic anaemia
Metabolic derangements in alcohol abuse
Hypertriglyceridemia Ketosis Hyperuricaemia Lactic acidosis Hypoglycemia
