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235 Cards in this Set
- Front
- Back
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Draw the adrenal cortex and medulla
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P. 280
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What is the primary regulatory control/anatomy/secretory products of the most superficial layer of adrenal cortex (under the capsule)?
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Control: Renin-angiotensin
Anatomy: Zona Glomerulosa Secretory: Aldosterone **Salt |
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What is the primary regulatory control/anatomy/secretory products of the 2nd most superficial layer of adrenal cortex?
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Control: ACTH, hypothalamic CRH
Anatomy: Zona Fasciculata Secretory: Cortisol, sex hormones **Sugar |
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What is the primary regulatory control/anatomy/secretory products of the layer of adrenal cortex closest to medulla?
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Control: ACTH, hypothalamic CRH
Anatomy: Zona Reticularis Secretory: Sex hormones (androgens) **Sex |
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What is the primary regulatory control/anatomy/secretory products of the adrenal medulla?
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Control: Preganglionic sympathetic fibers
Anatomy: Medulla Secretory: Catecholamines (epi, NE) |
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What is the most common tumor of the adrenal medulla in adults?
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Pheochromocytoma
Causes episodic hypertension |
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What is the most common tumor of the adrenal medulla in kids?
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Neuroblastoma
Does NOT cause episodic hypertension |
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How do the adrenal glands drain?
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Left adrenal --> Left adrenal vein --> Left renal vein --> IVC
Right adrenal --> Right adrenal vein --> IVC Same as left and right gonadal vein |
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Name 2 parts of the pituitary gland
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Posterior pituitary (neurohypophysis)
Anterior pituitary (adenohypophysis) |
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What does the posterior pituitary do?
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Neurohypophysis --> vasopressin (ADH) and oxytocin, made in the hypothalamus and shipped to pituitary
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What is posterior pituitary derived from?
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Neuroectoderm
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What does the anterior pituitary do?
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Adenohypophysis --> FSH, LH, ACTH, TSH, prolactin, GH, melanotropin (MSH)
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What is anterior pituitary derived from?
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Oral ectoderm
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What is the hormonal alpha subunit?
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Common subunit to TSH, LH, FSH, and hCG
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What is the hormonal beta subunit?
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Determines hormonal specificity
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Name 2 acidophilic hormones
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GH
Prolactin |
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Name 4 basophilic hormones
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FSH
LH ACTH TSH |
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What are the islets of Langerhans?
Where do they come from? |
Collections of alpha, beta, and gamma endocrine cells (most numerous in tail of pancreas)
Islets arise from pancreatic buds |
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What do alpha endocrine cells make?
Where are they located? |
Glucagon
Peripheral |
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What do beta endocrine cells make?
Where are they located? |
Insulin
Central |
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What do gamma endocrine cells make?
Where are they located? |
Somatostatin
Interspersed |
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Draw the endocrine pancreas cell types
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P. 280
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What are the insulin-dependent organs and how do they get glucose?
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Skeletal muscle and adipose tissue depend on insulin for increased glucose uptake (GLUT-4)
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What are the insulin-independent organs and how do they get glucose?
What do they rely on? |
Brain and RBCs take up glucose independent of insulin levels (GLUT-1)
Brain depends on glucose for metabolism under normal circumstances and uses ketone bodies in starvation RBCs always depend on glucose |
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What does prolactin do to dopamine?
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Increases dopamine synthesis and secretion from hypothalamus
Dopamine inhibits prolactin secretion |
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What do dopamine agonists/antagonists do to prolactin?
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DA agonists (bromocriptine): Inhibit prolactin secretion
DA antagonists (most antipsychotics): Stimulate prolactin secretion |
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What does prolactin do in females?
Prolactinomas? |
Inhibits GnRH synthesis and release, which inhibits ovulation
Amenorrhea is commonly seen in prolactinomas |
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Draw the HP axis for prolactin
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P. 281
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Name 7 hypothalamic-pituitary hormones and what they regulate
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TRH--> TSH, prolactin
Dopamine inhibits prolactin CRH --> ACTH GHRH --> GH Somatostatin inhibits GH, TSH GnRH --> FSH, LH Prolactin inhibits GnRH |
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Draw the pathway of adrenal steroids
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P. 282
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Name 3 effects of 17alpha hydroxylase deficiency
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Decreased sex hormones
Decreased cortisol Increased mineralcorticoids |
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Name 2 symptoms of 17alpha hydroxylase deficiency
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Hypertension
Hypokalemia |
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What happens in males as a result of 17alpha hydroxylase deficiency?
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Decreased DHT --> Pseudohermaphroditism (essentially phenotypic females, no internal reproductive structures due to MIF)
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What happens to females as a result of 17alpha hydroxylase deficiency?
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Externally phenotypic female with normal internal sex organs, but lacking secondary sexual characteristics (sexual infantilism)
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What happens in 21alpha hydroxylase deficiency?
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Most common form
Decreased cortisol (increased ACTH) Decreased mineralocorticoids Increased sex hormones |
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Name 7 symptoms of 21alpha hydroxylase deficiency
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Masculinization
Female psydohermaphroditism Hypotension Hyperkalemia Increased plasma renin activity Volume depletion Salt wasting can lead to hypovolemic shock in the newborn |
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What happens in 11beta-hydroxylase deficiency?
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Decreased cortisol
Decreased aldosterone and corticosterone Increased sex hormones |
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Name 2 symptoms of 11beta-hydroxylase deficiency
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Masculinization
Hypertension (like aldosterone, 11-deoxycorticosterone is a mineralocorticoid and is secreted in excess) |
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Name 3 types of congenital bilateral adrenal hyperplasias
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17alpha hydroxylase deficiency
21alpha hydroxylase deficiency 11beta hydroxylase deficiency All congenital adrenal enzyme deficiencies are characterized by an enlargement of the adrenal glands due to an increase in ACTH stimulation because of the decreased levels of cortisol |
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What is the source of cortisol?
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Adrenal zona fasciculata
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Name 5 functions of cortisol
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Anti-inflammatory
Increases gluconeogenesis, lipolysis, proteolysis Decreases immune function Maintains BP Decreases bone formation |
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How is cortisol regulated?
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CRH (hypothalamus) stimulates ACTH release (pituitary), causing cortisol production in adrenal zona fasciculata
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What is cortisol bound to?
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Corticosteroid-binding globulin
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What induces prolonged secretion of cortisol?
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Chronic stress
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What is the source of PTH?
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Chief cells of parathyroid
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Name 4 functions of PTH
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Increase bone resorption of calcium and phosphate
Increase kidney resorption of calcium in distal convoluted tubule Decrease kidney reabsorption of phosphate Increase 1,25-(OH)2 vitamin D (calcitriol) production by stimulating kidney 1alpha-hydroxylase |
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Name 2 ways PTH is regulated
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Decreasing free serun Ca increases PTH secretion
Decreasing serum Mg decreases PTH secretion Common causes of decreased serum Mg = diarrhea, aminoglycosides, diuretics, alcohol abuse |
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What does PTH do?
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Increases serum Ca
Decreases serum (PO4) Increases urine (POF) Stimulates both osteoclasts and osteoblasts |
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Draw a diagram of calcium homeostasis
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P. 283
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What is the source of Vitamin D (cholecalciferol)?
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Vitamin D3 from sun exposure in skin
D2 ingested from plants Both converted to 25-OH Vit D in liver and to 1,25-(OH)2 Vit D (active form) in kidney |
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Name 3 functions of Vitamin D
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Increases absorption of dietary calcium
Increases absorption of dietary phosphate Increases bone resorption of Ca and (PO4)3- |
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Name 4 ways Vitamin D is regulated
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Increased PTH causes increased 1,25-(OH)2 Vitamin D production
Decreased Ca increases 1,25-(OH)2 Vitamin D production Decreased phosphate causes increased 1,25-(OH)2 Vitamin D production 1,25-(OH)2 Vitamin D feedback inhibits its own production |
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What happens if you do not get Vitamin D?
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Kids: Rickets
Adults: Osteomalacia |
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What is 24,25-(OH)2 Vitamin D?
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Inactive form of Vitamin D
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Compare PTH and 1,25-(OH)2 Vitamin D regulation
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PTH increases calcium reabsorption and decreases phosphate reabsorption
1,25-(OH)2 Vitamin D increases absorption of both calcium and phosphate |
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What is the source of calcitonin?
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Parafollicular cells (C cells) of thyroid
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What is the function of calcitonin?
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Decrease bone resorption of calcium
Opposes actions of PTH - not important in normal calcium homeostasis |
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How is calcitonin regulated?
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Increased serum Ca causes calitonin secretion
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Draw steroid/thyroid hormone mechanism
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P. 284
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Name 7 steroid/thyroid hormones
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Progesterone
Estrogen Testosterone Cortisol Aldosterone Thyroxine and T3 |
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What happens in men when levels of sex hormone-binding globulin increase?
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Lower free testosterone --> Gynecomastia
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What happens in women when levels of sex hormone-binding globulin decrease?
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Raises free testosterone --> Hirsutism
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How do steroid hormones circulate?
What delays their action? |
They are lipophilic and relatively insoluble in plasma - therefore, they must circulate bound to specific binding globulins, which increase solubility and allow for increased delivery of steroid to the target organ
Need for gene transcription and protein synthesis delays the onset of action of these hormones |
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What are T3/T4?
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Iodine-containing hormones that control the body's metabolic rate
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What is the source of T3/T4?
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Follicles of thyroid
Most T3 formed in blood |
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Name 5 functions of T3/T4
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Bone growth (synergism with GH)
CNS maturation Increased beta1 receptors in heart = increased CO, HR, SV, contractility Increased basal metabolic rate via increased Na/K ATPase activity = increased O2 consumption, RR, body temp Increased glycogenolysis, gluconeogenesis, lipolysis |
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How are T3/T4 regulated?
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TRH (hypothalamus) stimulates TSH (pituitary) which stimulates follicular cells
Negative feedback by free T3 to anterior pituitary decreases sensitivity to TRH |
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What does TSI do?
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Like TSH
Stimulates follicular cells (Graves' disease) |
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What does thyroxine-binding globulin do?
How does this impact activity? |
Binds most T3/T4 in blood
Only free hormone is active |
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When is TBG decreased?
When is TBC increased? |
Hepatic failure
Pregnancy (estrogen increases TBG) |
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What is the major thyroid product?
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T4
Converted to T3 by peripheral tissue T3 binds receptors with greater affinity than T4 |
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What is peroxidase?
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Enzyme responsible for oxidation and organification of iodide as well as coupling of MIT and DIT
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Draw the process of thyroid hormone production
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P. 285
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Name 11 endocrine hormones that use cAMP signaling
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FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2 receptor), MSH, PTH, Calcitonin, Glucagon
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Name 3 endocrine hormones that use cGMP signaling
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ANP
EDRF NO |
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Name 5 endocrine hormones that use IP3 signaling
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GnRH
GHRH Oxytocin ADH (V1 receptor) TRH |
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Name 7 endocrine hormones that use steroid receptor signaling
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Glucocorticoid
Estrogen Progesterone Testosterone Aldosterone Vitamin D T3/T4 |
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Name 6 endocrine hormones that use tyrosine kinase signaling
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Insulin
IGF-1 FGF PDGF Prolactin GH |
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What causes Cushing's syndrome?
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Increased cortisol
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Name 4 etiologies of Cushing's syndrome
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Pituitary adenoma (Cushing's disease): Increased ACTH
Adrenal hyperplasia/neoplasia: Decreased ACTH Ectopic ACTH production (ex. small cell lung cancer): Increased ACTH Iatrogenic (chronic steroid use): Decreased ACTH, most common etiology |
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Name 10 findings of Cushing's syndrome
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Hypertension, weight gain, moon facies, truncal obesity, buffalo hump, hyperglycemia (insulin resistance), skin changes (thinning, striae), osteoporosis, amenorrhea, and immune suppression
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What is a dexamethasone suppression test?
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Dex = synthetic glucocorticoid
Healthy: Decreased cortisol after low dose ACTH-producing pituitary tumor: Increased cortisol after low dose, decreased cortisol after high dose Ectopic ACTH-producing tumor: Increased cortisol after low dose, increased cortisol after high dose Cortisol producing tumor: Increased cortisol always |
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What is primary hyperaldosteronism (Conn's syndrome)?
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Caused by an aldosterone-secreting tumor, resulting in hypertension, hypokalemia, metabolic alkalosis, and low plasma renin
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What is secondary hyperaldosteronism?
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Due to renal artery stenosis, chronic renal failure, CHF, cirrhosis, or nephrotic syndrome
Kidney perception of low intravascular volume results in an overactive renin-angiotensin system; associated with high plasma renin |
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How is hyperaldosteronism treated?
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Spironolactone, a K+-sparing diuretic that works by acting as an aldosterone antagonist
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What is Addison's disease?
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Primary deficiency of aldosterone and cortisol due to adrenal atrophy or destruction by disease
**Adrenal Atrophy and Absence of hormone production - all 3 cortical divisions |
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What does Addison's disease cause?
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Hypotension (hyponatremic volume contraction)
Skin hyperpigmentation (due to MSH, a byproduct of increased ACTH production from POMC) |
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How do you distinguish secondary adrenal insufficiency from Addison's disease?
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Secondary adrenal insufficiency (decreased pituitary ACTH production) has no skin hyperpigmentation and no hyperkalemia
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What is Waterhouse-Friderichsen syndrome?
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Acute adrenocortical insufficiency due to adrenal hemorrhage associated with meningococcal septicemia
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What is Sheehan's syndrome?
Cause Effects |
Postpartum hypopituitarism
Enlargement of anterior pituitary (increased lactotrophs) during pregnancy without corresponding increased blood supply leads to increased risk of infarction of the pituitary gland following severe bleeding and hypoperfusion during delivery May cause fatigue, anorexia, poor lactation, and loss of pubic/axillary hair |
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What is pheochromocytoma?
What is it derived from? |
Most common tumor of the adrenal medulla in adults
Derived from chromaffin cells (arise from neural crest) |
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What do pheochromocytomas secrete?
What can this cause? |
Epinephrine
NE Dopamine Can cause episodic hypertension |
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What is urinary VMA?
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Breakdown product of norepinephrine
VMA and catecholamines are elevated in urine |
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Name 3 things pheochromocytoma is associated with?
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Neurofibromatosis
MEN type 2A and 2B |
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How is pheochromocytoma treated?
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Alpha-antagonists
Especially phenoxybenzamine, a nonselective irreversible alpha-blocker |
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Name 5 episodic hyperadrenergic symptoms
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Pressure (elevated BP)
Pain (headache) Perspiration Palpitations (tachycardia) Pallor Symptoms occur in "spells" - relapse and remit |
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What is the rule of 10's in pheochromocytoma?
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10% malignant
10% bilateral 10% extra-adrenal 10% calcify 10% kids 10% familial |
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Draw out the pathway from tyrosine to epinephrine
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P. 287
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What is neuroblastoma?
Where does it occur? |
Most common tumor of the adrenal medulla in kids
Can occur anywhere along the sympathetic chain |
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What do you find in neuroblastoma?
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HVA (breakdown product of DA) in urine
Less likely to develop hypertension N-myc oncogene |
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Name 4 characteristics of MEN 1 (Werner's syndrome)
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Parathyroid tumors
Pituitary tumors (prolactin or GH) Pancreatic endocrine tumors - Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas (rare) Commonly presents with kidney stones and stomach ulcers |
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Name 3 characteristics of MEN 2A (Sipples' syndrome)
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Medullary thyroid carcinoma (secretes calcitonin)
Pheochromocytoma Parathyroid tumors |
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Name 3 characteristics of MEN 2B
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Medullary thyroid carcinoma (secretes calcitonin)
Pheochromocytoma Oral/intestinal ganglioneuromatosis (associated with marfanoid habitus) |
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What does MEN stand for?
How is it transmitted? |
Multiple endocrine neoplasias
All MEN syndromes = autosomal-dominant inheritance |
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Name a gene associated with MEN
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ret gene in MEN 2A and 2B
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Name 12 symptoms of hypothyroidism
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Cold intolerance, hypoactivity, weight gain, fatigue, lethargy, decreased appetite, constipation, weakness, decreased reflexes, myxedema (facial/periorbital), dry/cool skin, coarse/brittle hair
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How are other hormones affected in hypothyroidism?
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Increased TSH (sensitive test for primary hypothyroidism)
Decreased total T4 Decreased free T4 Decreased T3 uptake |
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Name 9 symptoms of hyperthyroidism
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Heat intolerance, hyperactivity, weight loss, chest pain/palpitations, arrhythmias, diarrhea, increased reflexes, warm/moist skin, fine hair
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How are other hormones affected in hyperthyroidism?
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Decreased TSH (if primary)
Increased total T4 Increased free T4 Increased T3 uptake |
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What is Hashimoto's thyroiditis?
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Autoimmune disorder resulting in hypothyroidism (can have thyrotoxicosis during follicular rupture)
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What do you find in Hashimoto's thyroiditis?
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Slow course
Moderately enlarged, nontender tyroid Lymphocytic infiltrate with germinal centers Antimicrosomal and antithyroglobulin antibodies Associated with Hurthle cells on histology |
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What is subacute thyroiditis (de Quervain's)?
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Self-limited hypothyroidism often following a flulike illness - may be hyperthyroid early in course
Elevated ESR, jaw pain, early inflammation, and very tender thyroid gland (lymphocytic subacute thyroiditis is painless) Histology shows granulomatous inflammation |
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What is Riedel's thyroiditis?
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Thyroid replaced by fibrous tissue (hypothyroid)
Presents with fixed, hard, and painless goiter |
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What is Graves' disease?
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Autoimmune hyperthyroidism with thyroid-stimulating/TSH receptor antibodies - Type II hypersensitivity
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Name 3 symptoms of Graves' disease
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Ophthalmopathy (proptosis, EOM swelling)
Pretibial myxedema Diffuse goiter Often presents during stress |
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How does Graves' disease kill you?
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Stress-induced catecholamine surge leading to death by arrhythmia
Serious complication of Graves' and other hyperthyroid disorders |
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What is toxic multinodular goiter?
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Iodine deprivation followed by iodine restoration
Causes release of T3 and T4 Nodules are not malignant |
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What is Jod-Basedow phenomenon in toxic multinodular goiter?
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Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete
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Name 5 kinds of thyroid cancer
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Papillary carcinoma
Follicular carcinoma Medullary carcinoma Undifferentiated/anaplastic Lymphoma |
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What is the prognosis for papillary carcinoma of thyroid?
What cell findings are there? Who is at risk? |
Most common
Excellent prognosis "Ground glass" nuclei (Orphan Annie) Psammoma bodies Nuclear grooves Increased risk with childhood irradiation |
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What is the prognosis for follicular carcinoma of thyroid?
What do follicles look like? |
Good prognosis
Uniform follicles |
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Where does medullary carcinoma of thyroid come from?
What does it produce? What does it look like? What is it associated with? |
Parafollicular C cells
Produces calcitonin Sheets of cells in amyloid stroma Associated with MEN types 2A and 2B |
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What is the prognosis for undifferentiated/anaplastic thyroid cancer?
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Older patients
Very poor prognosis |
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What is lymphoma associated with?
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Hashimoto's thyroiditis
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Name 2 types of cretinism and what causes them
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Due to severe fetal hypothyroidism
Endemic cretinism occurs wherever endemic goiter is prevalent (lack of dietary iodine) Sporadic cretinism is cause by defect in T4 formation or developmental failure in thyroid formation |
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Name 5 findings of cretinism
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Pot-belly
Pale Puffy face Protruding umbilicus Protuberant tongue |
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What is acromegaly due to?
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Excess GH in adults
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Name 5 findings of acromegaly
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Large tongue with deep furrows
Deep voice Large hands and feet Coarse facial features Impaired glucose tolerance (insulin resistance) |
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Excess GH in adults causes ______
Excess GH in children causes _____ |
Acromegaly
Gigantism |
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What is the treatment for acromegaly?
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Pituitary adenoma resection followed by octreotide administration
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When is increased GH normal?
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Stress
Exercise Hypoglycemia |
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How do you diagnose acromegaly?
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Increased serum IGF-1
Failure to suppress serum GH following oral glucose tolerance test |
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What is primary hyperparathyroidism?
Cause Findings Symptoms |
Usually an adenoma
Hypercalcemia, hypercalciuria (renal stones), hypophosphatemia, Increased PTH/alkaline phosphatase/ cAMP in urine Often asymptomatic or may present with weakness and constipation |
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What is secondary hyperparathyroidism?
Cause Findings |
Hyperplasia due to decreased gut Ca absorption and increased phosphorus
Most often occurs in chronic renal disease (causes hypovitaminosis D --> decreased Ca absorption) Hypocalcemia, hyperphosphatemia, increased alkaline phosphatase, increased PTH |
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what is osteitis fibrosa cystica (von Recklinghausen's syndrome)?
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Cystic bone spaces filled with brown fibrous tissue (bone pain)
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What is renal osteodystrophy?
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Bone lesions due to secondary hyperparathyroidism due in turn to renal disease
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Name 3 things hypoparathyroidism is due to
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Accidental surgical excision (thyroid surgery)
Autoimmune destruction DiGeorge syndrome |
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Name 4 signs of hypoparathyroidism
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Hypocalcemia
Tetany Chvostek's sign Trousseau's sign |
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What is Chvostek's sign?
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Tapping of facial nerve --> contraction of facial muscles
Hypoparathyroidism |
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What is Trousseau's sign?
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Occlusion of brachial artery with BP cuff --> carpal spasm
Hypoparathyroidism |
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What is pseudohypoparathyroidism?
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Autosomal dominant kidney unresponsiveness to PTH
Hypocalcemia, shortened 4th/5th digits, short stature |
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Name 12 things that can cause hypercalcemia
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Calcium ingestion (milk-alkali syndrome), hyperparathyroid, hyperthyroid, iatrogenic (thiazides), multiple myeloma, Paget's disease, Addison's disease, neoplasms, Zollinger-Ellison syndrome, excess vitamin D, excess vitamin A, sarcoidosis
**CHIMPANZEES |
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What is pituitary adenoma?
Name 4 findings What else can happen? |
Most commonly prolactinoma
Amenorrhea, galactorrhea, low libido, infertility Can impinge on optic chiasm --> bitemporal hemianopia |
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Name 2 agents that can cause shrinkage of pituitary adenoma
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Bromocriptine or cabergoline (DA agonists)
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Name 7 acute manifestations of diabetes mellitus
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Polydipsia, polyuria, polyphagia, weight loss, DKA (type 1), hyperosmolar coma (type 2), unopposed secretion of GH and epinephrine (exacerbating hyperglycemia)
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Draw the path from insulin deficiency to coma/death
|
P. 290
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Name two types of chronic manifestations of diabetes mellitus
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Nonenzymatic glycosylation
Osmotic damage |
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Name 2 types of nonenzymatic glycosylation chronic manifestations of diabetes mellitus
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Small vessel disease
Large vessel atherosclerosis |
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What happens in small vessel disease in diabetes mellitus?
|
Diffuse thickening of basement membrane --> retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation), glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to hypertension, Kimmelstiel-Wilson nodules)
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What happens in large vessel disease in diabetes mellitus?
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Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease and gangrene, cerebrovascular disease
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Name 2 things that happen via osmotic damage in diabetes mellitus
|
Neuropathy (motor, sensory, and autonomic degeneration)
Cataracts (sorbitol accumulation) |
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Name 3 tests for diabetes mellitus
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Fasting serum glucose
Glucose tolerance test HbA1c (measures long-term diabetic control) |
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Type 1 vs type 2 diabetes mellitus: What is the primary defect?
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1: Viral or immune destruction of beta cells
2: Increased resistance to insulin |
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Type 1 vs type 2 diabetes mellitus: Is insulin necessary in treatment?
|
1: Always
2: Sometimes |
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Type 1 vs type 2 diabetes mellitus: What age do they occur (exceptions are common)?
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1: < 30
2: > 40 |
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Type 1 vs type 2 diabetes mellitus: Association with obesity?
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1: No
2: Yes |
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Type 1 vs type 2 diabetes mellitus: Genetic predisposition?
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1: No
2: Yes |
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Type 1 vs type 2 diabetes mellitus: Association with HLA system?
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1: Weak, polygenic
2: Strong, polygenic |
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Type 1 vs type 2 diabetes mellitus: Glucose intolerance?
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1: Severe
2: Mild to moderate |
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Type 1 vs type 2 diabetes mellitus: Ketoacidosis?
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1: Common
2: Rare |
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Type 1 vs type 2 diabetes mellitus: Beta-cell numbers in the islets?
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1: Decreased
2: Variable (with amyloid deposits) |
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Type 1 vs type 2 diabetes mellitus: Serum insulin level?
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1: Decreased
2: Variable |
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Type 1 vs type 2 diabetes mellitus: Classic symptoms of polyuria, polydipsia, thirst, weight loss?
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1: Common
2: Sometimes |
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What is diabetic ketoacidosis?
|
One of the most important complications of type I diabetes
Usually due to increased insulin requirements from increased stress (ex. infection) - excess fat breakdown and increased ketogenesis from increased free fatty acids, which are then made into ketone bodies (beta-hydroxybutyrate >acetoacetate) |
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Name 6 signs/symptoms of DKA
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Kussmaul respirations (rapid/deep breathing)
Nausea/vomiting Abdominal pain Psychosis/delirium Dehydration Fruity breath odor (due to exhaled acetone) |
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What do labs look like in DKA?
|
Hyperglycemia, increased H+, decreased HCO3- (anion gap metabolic acidosis), increased blood ketone levels, leukocytosis,
Hyperkalemia, but depleted intracellular K+ due to transcellular shift from decreased insulin |
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Name 5 complications of DKA
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Life-threatening mucormycosis
Rhizopus infection Cerebral edema Cardiac arrhythmias Heart failure |
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Name 4 treatments of DKA
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Fluids
Insulin K+ (to replete intracellular stores) Glucose if necessary to prevent hypoglycemia |
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What is diabetes insipidus?
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Characterized by intense thirst and polyuria together with an inability to concentrate urine owing to lack of ADH (central DI - pituitary tumor, trauma, surgery, histiocytosis X) or to a lack of renal response to ADH (nephrogenic DI - hereditary of secondary to hypercalcemia, lithium, demeclocycline - ADH antagonist)
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How is diabetes insipidus diagnosed?
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Water deprivation test - urine osmolality doesn't increase
Response to desmopressin distinguishes between central and nephrogenic |
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Name 2 findings in diabetes insipidus
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Urine specific gravity < 1.006
Serum osmolality > 290 mOsm/L |
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What is the treatment for diabetes insipidus?
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Adequate fluid intake
For central DI - intranasal desmopressin (ADH analog) For nephrogenic DI - hydrochlorothizaide, indomethacin, or amiloride |
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What is SIADH?
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Syndrome of inappropriate antidiuretic hormone secretion
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Name 3 effects of SIADH
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Excessive water retention
Hyponatremia Urine osmolarity > serum osmolarity Very low serum sodium levels can lead to seizures (correct slowly) |
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Name 4 causes of SIADH
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Ectopic ADH (small cell lung cancer)
CNS disorders/head trauma Pulmonary disease Drugs (ex. cyclophosphamide) |
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Name 2 treatments for SIADH
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Demeclocycline
H2O restriction |
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What is carcinoid syndrome?
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Rare syndrome caused by carcinoid tumors (neuroendocrine cells), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT)
Not seen if tumor is limited to GI tract (5-HT undergoes first-pass metabolism in liver) |
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Name 4 things carcinoid syndrome causes
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Recurrent diarrhea
Cutaneous flushing Asthmatic wheezing Right-sided valvular disease |
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What is the most common tumor of appendix?
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Carcinoid - derived from neuroendocrine cells of GI tract
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What is seen in the urine with carcinoid syndrome?
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Increased 5-HIAA
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What is the rule of 1/3s in carcinoid syndrome?
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1/3 metastasize
1/3 present with secondary malignancy 1/3 multiple |
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What is the treatment for carcinoid syndrome?`
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Octreotide
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What is Zollinger-Ellison syndrome?
What does it cause? What is it associated with? |
Gastrin-secreting tumor of pancreas or duodenum
Causes recurrent ulcers May be associated with MEN type 1 |
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What is the treatment strategy for type 1 DM?
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Low-sugar diet
Insulin replacement |
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What is the treatment strategy for type 2 DM?
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Dietary modification and exercise for weight loss
Oral hypoglycemics Insulin replacement |
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Name 7 classes of drugs used in diabetes (both types)
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Insulin
Sulfonylureas Biguanides Glitazones alpha-glucosidase inhibitors Mimetics GLP-1 mimetics |
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Name 6 kinds of insulin and how long they act
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Lispro (short)
Aspart (short) Regular (short) NPH (intermediate) Glargine (long) Detemir (long) |
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What is the action of insulin in liver, muscle, fat?
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Bind insulin receptor (tyrosine kinase activity)
Liver: Increase glucose stored as glycogen Muscle: Increase glycogen and protein synthesis, K+ uptake Fat: Aids TG storage |
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What is the clinical use of insulin?
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Type 1 DM, type 2 DM
Also life-threatening hyperkalemia and stress-induced hyperglycemia |
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Name 2 toxicities of insulin
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Hypoglycemia
Hypersensitivity reaction (very rare) |
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Name 5 sulfonylureas
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First generation: Tolbutamide, Chlorpropamide
Second generation: Glyburide, Glimepiride, Glipizide |
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What is the action of sulfonuylureas?
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Close K+ channel in beta-cell membrane, so cell depolarizes --> triggering of insulin release via increased Ca influx
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What is the clinical use of sulfonylureas?
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Stimulate release of endogenous insulin in type 2 DM
Requires some islet function, so they are useless in type 1 DM |
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Name 2 toxicities of sulfonylureas
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First generation: Disulfiram-like effects
Second generation: Hypoglycemia |
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Name a biguanide
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Metformin
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What is the action of metformin?
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Exact mechanism unknown
Possibly decreases gluconeogenesis, increases glycolysis, decreases serum glucose levels Overall acts as insulin sensitizer |
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What is the clinical use of metformin?
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Used as oral hypoglycemic
Can be used in patients without islet function |
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What is a toxicity of metformin?
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Most grave adverse effect is lactic acidosis
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Name 2 glitazones
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Pioglitazone
Rosiglitazone |
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What do glitazones do?
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Increase target cell response to insulin
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What is the clinical use of glitazones?
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Used as monotherapy in type 2 DM or in combo with other diabetic agents
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Name 4 toxicities of glitazones
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Weight gain
Edema Hepatotoxicity CV toxicity |
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Name 2 alpha-glucoside inhibitors
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Acarbose
Miglitol |
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What is the action of alpha-glucosidase inhibitors?
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Inhibit intestinal brush border alpha-glucosidases
Delayed sugar hydrolysis and glucose absorption leads to decreased postprandial hyperglycemia |
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What is the clinical use of alpha-glucosidase inhibitors?
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Used as monotherapy in type 2 DM or in combo with other diabetic drugs
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Name a toxicity of alpha-glucosidase inhibitors
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GI disturbances
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Name a mimetic
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Pramlintide
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What is the action of pramlintide?
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Decrease glucagon
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What is the clinical use of pramlintide?
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Type 2 DM
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Name 3 toxicities of pramlintide
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Hypoglycemia
Nausea Diarrhea |
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Name a GLP-1 mimetic
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Exanatide
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Name 2 actions of exanatide
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Increased insulin
Decreased glucagon release |
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What is the clinical use of exanatide?
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Type 2 DM
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Name 3 toxicities of exanatide (one questionable)
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Nausea
Vomiting ? pancreatitis |
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What is the mechanism of orlistat?
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Alters fat metabolism by inhibiting pancreatic lipases
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What is the clinical use of orlistat?
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Long-term obesity management (in conjunction with modified diet)
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Name 4 toxicities of orlistat
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Steatorrhea
GI discomfort Reduced absorption of fat-soluble vitamins Headache |
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What is the mechanism of sibutramine?
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Sympathomimetic serotonin and norepinephrine reuptake inhibitor
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What is the clinical use of sibutramine?
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Short-term and long-term obesity management
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Name 2 toxicities of sibutramine
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Hypertension
Tachycardia |
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What is the mechanism of propylthiouracil, methimazole?
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Inhibit organification and coupling of thyroid hormone synthesis
Propylthiouracil also decreases peripheral conversion of T4 to T3 |
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What is the clinical use of propylthiouracil, methimazole?
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Hyperthyroidism
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Name 3 toxicities of propylthiouracil, methimazole
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Skin rash
Agranulocytosis (rare) Aplastic anemia |
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What are 2 clinical uses of GH?
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GH deficiency
Turner's syndrome |
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What are 4 clinical uses of somatostatin (octreotide)?
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Acromegaly
Carcinoid Gastrinoma Glucagonoma |
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What are 4 clinical uses of oxytocin?
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Stimulates labor
Stimulates uterine contractions Stimulates milk let-down Controls uterine hemorrhage |
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What is the clinical use of ADH (desmopressin)?
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Pituitary (central, not nephrogenic) diabetes insipidus
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What is the mechanism of levothyroxine, triiodothyronine?
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Thyroxine replacement
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What are 2 clinical uses of levothyroxine, triiodothyronine?
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Hypothyroidism
Myxedema |
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Name 4 toxicities of levothyroxine, triiodothyronine
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Tachycardia
Heat intolerance Tremors Arrhythmias |
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Name 5 glucocorticoids
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Hydrocortisone
Prednisone Triamcinolone Dexamethasone Beclomethasone |
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What is the mechanism of glucocorticoids?
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Decrease the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2
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Name 4 clinical uses of glucocorticoids
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Addison's disease
Inflammation Immune suppression Asthma |
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What is a toxicity of glucocorticoids?
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Iatrogenic Cushing's syndrome - buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic)
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Demeclocycline
Mechanism 2 clinical uses 3 toxicities |
ADH antagonist (member of tetracycline family)
Clinical Use: Diabetes insipidus, SIADH Toxicities: Photosensitivity, abnormalities of bone and teeth |
