Anatomical pathology Flashcards
(113 cards)
General approach to endocrine and metabolism disorders
Recognise/think of possibility of endocrine disorder
Confirm quantitatively with testing
Investigate cause
Manage
Functions of endocrine organs
Growth, reproduction, energy metabolism, stress responses, electrolyte and water handling, mineral metabolism
Common symptoms in endocrine disorders
- weight change
- lethargy
- BP high or low
- fractures
- electrolyte/mineral changes
Clinical consequences of pituitary pathology
Mechanical:
- raised ICP
- bony erosion
- local pressure
Altered hormonal secretion:
- hyperpituitarism
- hypopituitarism
Hypopituitarism
Inadequate functional tissue
• Absence or destruction of pituitary Bssue
e.g. injury, ischaemia, infec/on, pressure from adjacent tumour,
Rathke’s cleA cyst, trauma, previous surgery or radiotherapy
• Sheehan’s syndrome: post partum hypopituitarism (enlarged ant pit during pregnancy, intra or post partum haemorrhage leads to ischaemia of pituitary)
• Simmond’s syndrome: hypopituitarism due to other causes
Lack of stimulus driving secreBon (e.g. hypothalamic disease)
Hyperfunc/on of one product may be associated with Hypofunc/on of others (as a result of ‘pressure’ atrophy), and pituitary hypofuncBon leads to secondary hypofuncBon of pituitary dependent endocrine glands (through feedback inhibiBon).
Hyperpituitarism
• Excess secretion of trophic hormones • Can be caused by: – Pituitary adenoma – Secondary hyperplasia – Pituitary carcinoma (rare) – Secretion of hormones by non-pituitary tumours – Hypothalamic disorders
Posterior pituitary syndromes
(1) Diabetes insipidus: passage of large volumes of dilute urine
2 main forms:
- central - decreased ADH secretion
- nephrogenic - ADH resistance in the kidney
(2) Syndrome of inappropriate ADH secretion
- resorption of XS amounts of water
- usually caused by ectopic ADH secretion
Clinical consequences of thyroid disease
Mechanical
• Thyroid enlargement = ‘goitre’ (unilateral, bilateral, localised, diffuse), usually not painful
• Compression effects (airway, oesophagus, large vessels, nerves)
Functional
• Hyperthyroidism
• Hypothyroidism
• Euthyroid
Examples of hyper plastic, neoplastic and inflammatory thyroid pathologies
Hyperplasia
– Diffuse / Graves (Autoimmune)
– Mul2nodular goitre / Nodular colloid goitre
Neoplasia
– Adenomas
• Follicular/HurthleCell/Other – Carcinomas
• Papillary/Follicular/Anaplastic/Medullary
Inflammatory
– Hashimoto (Autoimmune)
– Lymphocytic, Granulomatous (De Queryvain)
Cause of hypothyroidism
Defect anywhere in the hypothalamic-pituitary-thyroid axis
- iodine deficiency
- thyroiditis (hashimoto’s, lymphocytic)
Children: cretinism (iodine deficiency usually)
Adults: myxoedema (TSH raised if normal feedback inhibition is lost)
Hashimoto’s thyroiditis
Autoimmune disease - anti-TPO found
Symptoms and signs of hyperthyroidism
Symptoms:
– Nervousness, Anxiety, Increasedperspiration, – Heat intolerance, Hyperactivity,
– Palpitations
Signs
– Tachycardia or atrial arrhythmia
– Systolic hypertension with wide pulse pressure
– Warm, moist, smooth skin
– Lid lag
– Stare
– Hand tremor
– Muscle weakness
– Weight loss despite increased appetite (although a few patients may gain weight, if excessive intake outstrips weight loss)
– Reduction in menstrual flow or oligomenorrhea
Most common causes of hyperthyroidism
- Grave’s disease
- Multi nodular goitre (hyper functional)
- thyroid adenoma (hyper functional)
Grave’s disease antibodies and diagnosis
Auto-antibodies against TSH receptor and other thyroid antibodies
- presence of these antibodies indicates Grave’s
Actions of PTH
Bone resorption
Renal tubular resorption of calcium
Increases conversion of Vit D to active (hydroxy) form in kidney
With Vitamin D, promotes calcium resorption from small intestine
Increases urinary phosphate excretion causing phosphaturia
Net effect is to increase serum calcium
Common cause of chronic hypocalcaemia
Usually due to chronic renal failure, vitamin D deficiency, drugs or intestinal malabsorption of calcium
Signs/symptoms of hypocalcaemia
Convulsions, arrhythmias, tetany, numbness and parasthesia, cramps, fatigue, depression, altered cognition
Most common causes of hypercalcaemia and clinical manifestations
- hyperparathyroidism
- hypercalcaemia of malignancy - adenoma
Clinical - renal stones, bones (pain, arthritis), groans (confusions, lethargy, weakness) and moans (nausea, vomiting, weight gain or anorexia, pain)
4 Classifications of hyperparathyroidism
Primary HP: XS PTH production
Secondary HP: other disease process drives increased PTH levels
Tertiary HP: autonomous PTH secretion, caused by longstanding secondary HP
Ectopic secretion - paraneoplastic from other malignancies
MEN syndromes in endocrine disorders
MEN-1 - loss of tumour suppressor gene, primary hyperparathyroidism (adenoma or hyperplasia)
MEN-2 - medullary thyroid carcinoma is main manifestation, usually due to RET protocol-oncogene mutation
6 types of cells in the Islet’s of Langherans and their function
- β – Insulin (regulates glucose in tissues, reduces blood glucose)
- α - Glucagon (stimulates glycogenolysis in the liver, increases blood sugar)
• δ – Somatostatin (suppresses both insulin and glucagon release)
• PP – secretes pancreatic polypeptide (stimulates gastric and intestinal enzymes and inhibits intestinal motility)
– Also
• D1 – Vasoactive intestinal polypeptide (VIP), induces glycogenolysis and hyperglycaemia
• Enterochromaffin cells – Serotonin
Diagnosis criteria for Diabetes
- Fasting plasma glucose ≥ 126 mg/dL,
- Random plasma glucose ≥ 200 mg/dL (in a patient with classic hyperglycemic signs),
- 2-hour plasma glucose ≥ 200 mg/dL during an oral glucose tolerance test (OGTT) with a loading dose of 75 gm
- Glycated hemoglobin (HbA1C) level ≥ 6.5%
Clinical presentation of T2DM vs T1
T1: indolent onset (years) but sudden presentation (decompensation)
Polyuria, polydipsia, polyphagia, subsequently DKA
T2: unexplained fatigue, dizziness, blurred vision, often asymptomatic and may become hyperosmolar non-ketotic state
Pathogenesis of T1DM
¥ Develops in childhood, manifests at puberty, progresses with age
¥ Without exogenous insulin patients become ketotic → coma → death
¥ Interplay of genetics (esp HLA-DR3 or HLA-DR4) and environment (still unclear)
¥ β cell destruction follows loss of self tolerance for T cells specific islet antigens (insulin receptor, GAD, others)
o Autoreactive T cells are not removed
o Are able to attack islets
