Deck 1 Flashcards
- Q. What are the different classes of hormones?
A. Endocrine (blood bourne), paracrine (adjacent cells), autocrine (same cell feedback)
B. Peptides, monoamines - water soluble, binds to surface receptor of organ (short half life, fast clearance). Stored in granules.
C. Steroids, these are synthesized on demand, fat soluble so are protein bound in the blood, diffuse into the cell, bind to nucleus or cytoplasm receptor. Long half life and slow clearance.
- Q. Where is the pituitary gland located? What is the embryonic origin?
A. Sits on the sphenoid bone (in a saddle shaped depression called the sella turcica), in the cavernous sinus- very close to optic chiasm, hypothalamus, CN3,4,6, V1 and V2, internal carotid artery
B. Anterior pituitary: adenohypophysis develops from Rathke’s pouch, upward invagination of oral ectoderm from the roof of the stomedeum
C. Posterior pituitary: neurohypophysis develops from the infundibulum, downward extension of neural ectoderm from the floor of the dicephalon
- Q. What hormones does the pituitary gland release?
Anterior: FSH, LH, ACTH (adrenocorticotropic), TSH, Prolactin, GH
Posterior pituitary: ADH, oxytocin
- Q. What are the effects of GH?
Direct effects: breaks down fat, carb metabolism (increases blood glucose and other anti-insulin effects)
Indirect effects: binds to liver cells producing insulin-like growth factor (IGF1) → skeletal, increase cartilage formation and skeletal growth, also → extraskeletal – increases protein synthesis, cell growth and proliferation
- Q. Describe the short-term and long-term effect of stress (adrenal hormones)
Short term: catecholaemines (epinephrine and norepinephrine) - HR increases, BP increase, bronchioles dilate, liver converts glycogen to glucose and releases glucose to blood, blood flow changes (away from digestion and urine output), metabolic rate increases
Long term stress response: hypothalamus releases CRH → anterior pituitary → ACTH is released and acts at the adrenal cortex → mineralocorticoids and glucocorticoids results in :
+Kidneys retain sodium and water, blood volume and BP rises
+Proteins and fats converted to glucose or broken down for energy, blood glucose increases, immune system suppressed
- Q. How does the hypothalamus affect the ovaries and testes? (describe the axis)
Hypothalamus: GnRH
Anterior pituitary: FSH, LH
In the testes: LH acts in Leydig cells, producing testosterone. FSH acts on sertoli cells producing inhibin (-ve feedback) and androgen-binding protein. (spermatogenesis occurs in sertoli cells)
In the ovaries: LH → acts on Theca cells, causing the conversion of cholesterol to androgen
FSH → acts on granulosa cells, causing conversion of androgen to oestrogen (via aromatase)
- Q. How may a pituitary tumour present?
Pressure on local structure - eg, optic nerve, could cause headaches, hydrocephalus, damage to visual fields- (bitemporal homonymous hemianopia- damage to optic chiasm) CN damage, CSF leakage
Pressure on normal pituitary e.g. hypopituitarism = pale, no body hair, central obesity
Functioning tumour
-Prolactinoma (produces lactin = periods stop, infertile)
-Acromegaly = thick skin, sweaty, greasy,
-Crushing syndrome - increase steroids, cotisol = short and fa
- Q. Name 3 types of functioning tumours: how may these patients present?
A. Prolactinoma: prolactin released, this switches off gonadoproteins → Periods stop, (mild contraception) PC: Galactorrhea (milky secretion from breasts) /Amenorrhoea/infertility, loss of libido, visual field defect Tx: easily treatable with dopamine agonists - switches of prolactin secretion and can cause shrinkage e.g. Cabergoline or bromocriptine
B. Cushing’s disease: increased ACTH from pituitary/or from a tumour. PC: small and fat, fractures, bleeding, stretch marks (dramatic, purple in colour)
Acromegaly and gigantism: tumour produces GH, can either present as acromegaly (in adulthood) or gigantism (before puberty).
C. Acromegaly: slow onset → thick skin, greasy, sweaty, prognathism, frontal bossing, large hands, bigger shoes, can lead to heart disease, or could present with carpal tunnel syndrome
- Q. Name 5 co-morbidities associated with acromegaly, what symptoms may a patient present with? Ix? Tx?
A. Presenting features: acral enlargement, arthralgias, maxillofacial changes, excessive sweating, headache, hypogonadal symptoms - due to GH in adulthood
B. Co-morbidities: HTN and heart disease, sleep apnea, insulin-resistant diabetes, arthritis, cerebrovascular events and headache
C. Ix: 75gm oral glucose tolerance test for diagnosis of acromegaly (GH levels increase over time, in a healthy individual GH decrease after around 1 hour), excluded if: IGF-1 is normal or GH < 0.4ng/ml
D. Tx: pituitary surgery, medical, radiotherapy
E. Medical: dopamine agonists e.g. cabergoline. Somatostatin analogues and growth hormone receptor antagonists.
- Q. Name 5 clinical features associated with prolactinoma
A. Functioning tumour secretes prolactin (can be massive, depends on tumour size), could also be due to a non-functioning tumour that compresses the pituitary stalk
B. Local effects of tumour: headache, visual field defect, CSF leak (rare)
C. Prolactin: menstrual irregularity/amenorrhoea, infertility, galactorrhoea (milky secretion from breasts), low libido, low testosterone in men
Ix: measure levels of prolactin
Tx: dopamine agonists e.g. cabergoline - tumour shrinkage
- Q. When does type 1 DM usually present? What is the pathophysiology?
A. Presents in childhood at 6 yrs and around puberty 10-14years, increasing incidence, no gender difference (weight loss, ketonuria, hyperglycemia)
B. Destruction of beta cells of the pancreas = no production of insulin
Type 1A: due to T-cell mediated autoimmune disease
High glucose levels produce high blood osmolarity, this means that the patient become dehydrated and has to drink lots, they also secrete large amounts of aldosterone
- Q. When does type 2 DM usually present? What is the pathophysiology?
Usually presents 40-59 years, main RF: age, obesity, FHx, ethnicity
Others: underactivity, overeating, obesity, genetic links, low birth weight, CVD, HTN, onset may be accelerated by stress, pregnancy, illness or certain drugs
Combination of insulin resistance and relative secretory failure of insulin, there is high blood glucose, 50% beta cell mass, amyloid deposition around the islets
- Q. What clinical features of seen in DM1? DM2?
DM1: weight loss, ketonurea, hyperglycaemia, presence of autoimmune products,
Other clinical features: polyuria/thirst, weight loss, weakness, nausea/vomiting, leg cramps, blurred vision, abdo pain, kusmaul breathing, dehydration, hypotension, cold extremities/peripheral cyanosis, tachycardia, hypothermia, smell of acetone, confusion/drowsiness/coma
DM2: polyuria/thirst, lack of energy, visual blurring, genital inflammation, weight loss. Usually present with HTN, obesity, hypertriglyceridemia, decreased HDL cholesterol and acanthosis nigricans
- Q. What is the most common complication of DM1? DM2? What are precipitate complications?
Patients with DM1 are at risk of diabetic ketoacidosis, cells cannot uptake glucose and so fatty acid are metabolised as an energy source. This produce ketoacids, once of which is acetoacetic acid which spontaneously breaks down to produce acetone. This causes generalised acidosis.
Hyperglycaemia, hyperketonaemia, metabolic acidosis, kidney/liver damage and hyperventilation are seen. (dehydration, Kussmaul’s respiration, decreased consciousness, breath smells of ketones)
DM2: hyperosmolar hyperglycamic state → stroke, MI, arterial thrombosis, retinopathy, diabetic foot, neuropathy, infections
Illness may precipitate complications as patients need 25% more insulin
(also local infections at insulin injection site)
- Q. How may DM be diagnosed?
Fasting (8 hours) plasma glucose > 7.0mmol/L
Random plasma glucose >11.1mmol/L (normal level is <7.8 so between these values = impaired glucose tolerance)
HbA1C > 48mmol/L (6.5%) often used in DM2 diagnosis (42-47, 6.1-6.5% is considered pre diabetes)
