Note: the following material is for personal use only see below for
Download 3.95 Mb.
|
Muscle-Energy DisordersMcArdle’s V muscle phosphorylase deficiency / pain, cramps and myoglobinuria on exertion Treatment: avoid exertion, glucose or fructose before exertion Type VII muscle phosphofructokinase deficiency / rare / mild hemolytic anemia / similar symptoms/treatment as McArdle’s Metabolism and Fluid Maintenance maintenance fluid: 100 ml/kg (1st 10 kg) / 50 ml/kg (2nd 10 kg) / 20 ml/kg (remaining kg’s) normal fluid maintenance: 1500-2000 ml/M2 100 ml fluid required per 100 cal expended, which is 110 cal/kg/day insensible loss is 45 ml / 100 cal 50-70 ml fluid / 100 cal for renal excretion of metabolic waste products Na 3 mEq / 100 cal K 2.5 mg/kg/day (?) Dehydration: mild (5% infant, 3% adult) moderate (10%, 6%), severe (15%, 9%) 285-295 mOsm/L 180 mg/dL glucose = 10 mOsm/L [normal contribution is 10 mOsm/L] breast fed infant – 6 stools/day at 2 wks Endocrine Pituitary Gland Pituitary Adenomas, Hypopituitary, Diabetes Insipidus, SIADH Thyroid ↑ Hyperthyroidism, ↓ Hypothyroidism, Thyroiditis, Thyroid Neoplasms, Thyroid Malformations Parathyroid ↑ Hyperparathyroid, ↓ Hypoparathyroid, Pseudohypoparathyroid, Parathyroid Hyperplasia, Parathyroid Neoplasms, MEN Adrenal ↑Cushing’s, ↑ Adrenal Hyperplasia, Adrenal Adenoma, Adrenal lymphoma ↓Adrenal Insufficiency, ↑Conn’s, CAH, McCune-Albright Adrenal Medulla pheochromocytoma, paraganglioma, neuroblastoma Diabetes Mellitus Pituitary Pituitary Labs Thyrotropin T3/T4 FTI Thyroid hormone binding index Cortisol Prolactin Alpha-subunit (TSH, FSH, LH) FSH Diabetes 1-2% in US / 7th leading COD / non-enzymatic glycosylation (advanced glycosylation end-product or AGE results in atherogenesis, increased capillary permeability) / intra-cellular hyperglycemia (swelling and opacity of lens, neuronal damage) Type 1 (10-20%) lack of insulin – only some impairment of insulin action/secretion (by hyperglycemia) / whites, European origin / associated with other autoimmune diseases 80% have antibodies, 0.3% incidence, 5-7% incidence with family history
impairment of insulin action/secretion (by hyperglycemia) type 2 – acanthosis from increased insulin levels Diagnosis: current standard is now > 126 on fasting glucose / GTT (oral glucose tolerance test) is out of fashion (exception is PCOS patients, which can have normal fasting yet positive/abnormal GTT) Renal: often develop CRF within 10 yrs / retinopathy and nephropathy develop together Metabolic syndrome (associated with atherosclerotic disease) Diagnosed by 3 of 5 criteria (abdominal obesity, high blood pressure, low HDL, high TG, insulin resistance) central obesity, may or may not have elevated lipids (small, dense LDL particles are more atherogenic, however), hyperandrogenism, increased coagulation from increased PAI1 (inhibitor of tPA) often occurs before abnormalities of sugar levels occur hyperinsulinemia decreases secretion of uric acid (not part of definition of metabolic syndrome but does cause hyperuricemia) Microangiopathy thick, leaky BM (PAS stain), hyalinized arteriolosclerosis, atherosclerosis Nephropathy both afferent and efferent arterioles / arteriolar hyalinization / UTI / glycosylation of basement membrane leads to membranous GN (5-15% by 10-15 yrs) / 50% have
proliferative / cotton wool / associated with increased floaters Neuropathy axonal and demyelinating Skin acanthosis nigricans (see other) yellow discoloration [pic] necrobiosis lipoidica diabeticorum [pic] [dermis] anterior leg / ulceration and hypopigmented scarring Treatment: whirlpool therapy, occlusive dressings, topical steroids, aspirin Lipid abnormalities (see below) Immunocompromise fungus (yeast, other) / mucormycosis Hypercoagulable State (increased post-MI mortality) Increased 2b3a receptor expression (2b3a are essential in treatment of DM w/ acute coronary syndrome) Increased plasminogen activator inhibitor (PAH) Increased blood viscosity (sheer stress on plaque) Other abnormalities in clotting factors Treatment: [see diabetes medications] [NEJM] Control Glucose various agents (from different class) work well in combination A1C measures glucose levels over last 2-3 months oral agents (alone or in combination) can achieve A1C of 7.5 in up to ½ of patients hemolytic anemia will artificially lower A1C Insulin requirement ↑ with stress, ↓ with exercise (insulin potentiated by exercise; esp. in type I DM) Insulin requirement over 1.5 units/kg suggests overtreatment, rebound hyperglycemia or Somogyi effect (insulin resistance is a less common reason) Dawn phenomenon – hyperglycemic? in the morning – is it rebound or do they need more insulin qAM / check sugar at 2 am at night (nadir of FBS is 2–3 am) to investigate (if low, you need to reduce qHS insulin, if high, you can increase qHS insulin) Glucose control in ICU setting is class I recommendation: DIGI-AMI showed 30% decrease in 1 yr mortality for post-AMI patients randomized to tight glucose control Protect Kidneys ACE inhibitors lower intraglomerular pressure and reduce hemodynamically mediated FSGN (Cr may rise slightly upon initiation 2o to decreased GFR) ARBs may provide additional protection (by direct anti-TGF-B action) remodeling glomeruli to reduce protein filtration (proteins damage glomerulus) protein restricted diets lipid lowering agents are also renal-protective Protect Heart Physicians Health Study ASA 325 mg qd reduced MI for DM by 60% over 5 yrs (versus 44% for general population) Hypertension Proteinuria: loss of antithrombin, protein C and S leads to hypercoagulable state renal failure (GFR actually increased early on due to microalbuminuria) papillary necrosis, pyelonephritis
9/06 current goal LDL < 100 mg/dL Retinopathy control hypertension; see ophthalmologist at least once a year Neuropathy control glucose, hypertension; see podiatrist; treat neuropathy (if not due to other causes) Diabetic ketoacidosis (DKA) Causes: infection, MI, stress/trauma, not enough insulin or drug effect (phenytoin, thiazides, cortisol), new-onset diabetes Presentation: Hyperglycemia polyuria, polydipsia, weight loss, visual blurring, mental status change Acidosis nausea, vomiting, abdominal pain, fatigue, malaise, dyspnea cardiovascular collapse most common COD in DKA Diagnosis: must differentiate from hyperosmolar nonketotic coma Workup: CXR, amylase/lipase, cardiac enzymes, ABG, other tests Exam: dehydration, Kussmaul’s respirations, fruity breath Labs: hyperglycemia (usu. > 250 mg/dL), ketonuria (can check b-hydroxybuturate etc too), anion gap acidosis, moderately elevated amylase – why?, hypokalemia results from increased K excretion with diuresis of (anionic) ketones Complications: mucormycosis of paranasal sinuses due to acidosis-induced block of iron binding to transferrin (provides fungus w/ iron) / vascular thrombosis from hypercoagulable state + intravascular contraction / cerebral edema / respiratory distress (like ARDS w/ low PCWP), fluid overload, acute gastric dilatation Treatment: Replace fluids: usu. 3-5 L (1-2 L NS over 1st 2 h, replacing volume takes precedence over free water deficit, but can switch to ½ NS if hypernatremia (goal is to correct total body water deficit 250-500 ml/h), can use lactated ringer’s to avoid hyperchloremic metabolic acidosis, which often occurs during/after treatment of DKA) Potassium: very tricky, must be careful, insulin Rx can make initial hyperkalemia become hypokalemia, but must be careful not to overcompensate, best way is to check q 1-2 h K levels until stable (add K to IVF once < 5 mEq/L) Insulin: 0.1 to 0.2 units/kg IV push then same each hour until normalized (or 50 U then 10-20U/hr), measure every hour (should aim for 80-100 mg/dL/h decrease) but use anion gap as a guide / avoid cerebral edema / give SC insulin 30 mins before stopping IV to avoid rebound acidosis Glucose: start infusion when glucose 250-300 (then decrease insulin to 0.05 U/kg/hr) / important because ketones don’t normalize until point at which patient may already become hypoglycemic (but you need to keep the insulin going until anion gap normalizes (< 12) (urine is free of ketones) Bicarbonate: controversial // try not to give bicarbonate unless pH is really low (i.e. patient is hyperventilating and about to tire out) as it can cause worsening of hypokalemia, paradoxical CNS acidosis, delay in ketone clearance Phosphate: give if < 1 mg/dL or moderate hypophosphatemia and respiratory problems Mg, Ca: prn Hyperosmolar nonketotic coma Elderly patients with Type II diabetes (often undiagnosed) Findings: more marked hyperglycemia > 1000 mg/dl / more severe dehydration (longer undiagnosed) / serum osmolality of > 320-370 may cause mental obtundation, seizures, focal neurological signs / lactic acidosis is a poor prognostic sign Treatment: similar to DKA, but replace fluids carefully to avoid precipitation of heart failure in underlying heart disease Alcoholic ketoacidosis Mechanism: ratio of NADH:NAD shifted in favor of unreduced NAD / causes anion gap metabolic acidosis from ketoacidosis and lactic acidosis Presentation: similar presentation as DKA Treatment: NS and glucose / insulin usually not necessary Pituitary Adenomas Microadenoma < 10 mm (⅓ can be missed even by MRI) / found in 20% of all autopsies / hemorrhage involving most of gland is called pituitary apoplexy / microadenoma can cause “stalk” hyperprolactinemia by interrupting the inhibitory dopaminergic tone between the hypothalamus and the pituitary gland. Macroadenoma may become invasive / may compress adjacent structures Note: must ask for specific views of pituitary by CT or MRI Chromophobe adenoma – most common in adults – rare in childhood Somatotropic (GH, PRL) [NEJM] 20% of pituitary tumors (macro>micro) / most are plurihormonal GH and PL Presentation: acromegaly, gigantism (enlargement of hands, feet, jaw, and forehead), skin tags, thickened skin (coarse facial features), arthritis or carpal tunnel syndrome may develop, the pituitary adenoma may cause headaches and visual loss, often h/o kidney stones Complications: increased cardiovascular disease (50% with left ventricular hypertrophy, HTN is common) Diagnosis: insulin challenge does not decrease GH serum insulin-like growth factor (somatomedin-C) screening test of choice (reflects average GH level over several days, whereas GH itself is pulsatile, diurnal, variable), then confirm with GTT or ITT oral glucose tolerance test GH should normally reduce to < 1-2 ng/ml insulin tolerance test GH should increase in response to insulin (analogous to cosyntropin stim test to rule out adrenal insufficiency) Treatment: transphenoidal resection (complete tumor resection with cure of acromegaly often impossible) / low GH (75% cure with surgery) / high GH (35% cure with surgery) / radiotherapy may reduce regrowth (also octreotride 100 µg SC tid reduces GH secretion) / +/- bromocriptine Prolactinoma (PRL) - benign 30%, most common pituitary tumor / primary hyperprolactinemia / serum PRL > 300 ug/ml ( > 100 is suggestive; must get MRI) Macro – male / micro – female Presentation for macro: ocular movement defect (5-10%), females: galactorrhea, males: sexual dysfunction/gynecomasita (15%) Ddx (elevated prolactin): prolactinoma, loss of dopaminergic inhibition (neuroleptics), post-seizure, stalk hyperprolactinemia, uremia Treatment (macro): resection (80% success, 20% relapse), radiation (highly efficacious but causes panhypopituitary syndrome) Treatment (micro): bromocriptine, resection (80% success, 40% relapse, 40% still fertile) Corticotrophic adenoma (ACTH) 15% of pituitary tumors / micro, basophilic / Crooke’s hyaline may accumulate in surrounding cells Cushing’s Disease (must also include diabetes, hypertension) 80% from pituitary adenoma (ACTH) / 20% from adrenal adenoma (cortisol) Diagnosis: dexamethasone suppresses micro, but NOT macroadenomas
5-15% of pituitary tumors / result in hypogonadism Presentation: signs of compression / male: decreased libido / female: no change Diagnosis: increased LH, FSH levels Treatment: surgery
Causes:
Neoplasm: adenoma, mets, lymphoma, Rathke’s cysts, germ cell tumors, gliomas (rare), craniopharyngioma (children) Inflammatory: meningitis (others?), sarcoidosis, other inflammatory Damage (see below): subarachnoid hemorrhage, cranial trauma, surgery/radiation therapy Null-cell adenomas 20% of pituitary adenomas / local mass effects (e.g. compression of stalk interfering with dopamine release stalk prolactinemia, which is only mild increase, unlike true prolactinoma) / will often be positive for alpha-subunit (TSH, FSH, LH) Sheehan’s syndrome post-partum pituitary necrosis (may present even years after pregnancy) / infarction of adenohypophysis from combination of hemorrhagic shock of delivery and blood supply compressed by pregnancy-related hypertrophy of pituitary / also caused by DIC, DM, arteritis, trauma Empty sella syndrome herniation through defect in diaphragma sella leads to atrophy / often can still produce normal amounts of pituitary hormones (even though sella appears empty on MRI; functional rim of pituitary tissue) / risk factors: female, obese, hypertension Presentation: asymptomatic or chronic headaches
Occurs in late pregnancy, post-partum / less commonly occurs in men, post-menopausal women Associated with autoimmune thyroiditis, adrenalitis, atrophic gastritis, Sjögren’s, SLE, Cogan’s, Takayasu’s
Either as part of above or sarcoidosis Posterior Pituitary Syndromes Physiology: ADH released in response to 1st osmolality and 2nd volume shift of 10% / also nausea, drugs Central Diabetes Insipidus (see nephrogenic DI) lack of ADH / lesion of neurohypophysis (supraoptic, paraventricular) Presentation: polyuria, polydipsia, thirst (often seek cold liquids to stimulate ADH release) Causes: tumor, histiocytosis, sarcoidosis, trauma Complications: hypernatremia Treatment: desmopressin Syndrome of Inappropriate ADH Release (SIADH) unregulated ADH release / excessive water reabsorption leads to hyponatremia half of elderly patients with hyponatremia, usually resolves following removal of the drug
PTH function usually transiently lost following thyroidectomy ↓Ca, Phos, Albumin, Mg (EtOH can decrease Mg) levothyroxin 1.6 ug/kg (recheck in 6-8 wks) Ca replacement (2-3 g/day) calcitriol (0.25 mg bid), Do not jump to replace thyroid hormone in complicated cases Illness and various drugs can lower T3 (T4 and TBG can also be decreased) Thyroid Function Studies TSH / normal [1-4] Lower TSH: recovery from severe illness, metoclopramide, dopamine and corticosteroids Increase TSH: chlorpromazine, haldol, and amiodarone
measures circulating bound (~99%) and unbound T4 / values vary with TBG (see below) equilibrium dialysis (gold standard of free T4 assays) or by immunometric techniques (influenced by serum levels of lipids, proteins, and certain drugs)
Bound to TBG (just like T4) / elevated in hyperthyroidism (usu. earlier and more than T4), useful in confusing cases (not as a screening test) Useful to diagnose: Thyrotoxicosis: increased T3, normal FTI Toxic nodular goiter: increased T3, normal or increased T4 Iodine deficiency: normal T3, possibly decreased T4 Serum thyroglobulin Elevated in thyroid cancer and thyrotoxicosis emanating from the thyroid gland Normal in thyrotoxicosis secondary to iatrogenic ingestion of thyroid hormone
T3 resin uptake (T3RU or R T3U) Indirectly measures amount of thyroid binding protein
T4 x T3RU / 100 (corrects for variations in protein binding) Reverse T3 measures in inactive metabolite of T4 / used to diagnose "euthyroid sick syndrome" (alteration in TSH secretion and peripheral thyroid hormone binding and metabolism 2o to severe nonthyroidal illness or stress) Radioactive Iodine Uptake (I-123 scan) Normal 24-hour (10-30%) Increased homogenous Graves’, iodine deficiency Increased heterogeneous multinodular goiter Increased single focus hot nodule Decreased uptake thyroiditis Ingestion of thyroid hormone (thyrotoxicosis factitia) increased serum T4 and serum T3R , but the RAI is decreased instead of increased as it would be in other causes of hyperthyroidism; Note: serum thyroglobulin levels also decrease in thyrotoxicosis factitia and increase in thyrotoxicosis emanating from the thyroid gland Pre ablative therapy, calculate the I131 dose needed to administer Note: I131 therapy actually increases the risk of exophthalmos (which was already small) Serology Anti-microsomal (also anti-TPO) 80-90% sensitive for thyroiditis (not causal) Anti-thyroglobulin Antibodies Anti-TSH receptor antibodies can be tested for (usually not necessary) Malformations Maldescent pyramidal lobe (common) / ectopic thyroid tissue (papillary carcinoma met if found w/in lymph node) Thyroglossal duct cysts predispose to infection / surgical removal Hyperthyroidism Graves, thyroid storm, infectious thyroiditis, hypothyroidism Causes of Hyperthyroidism Graves’ disease Toxic multinodular goiter Toxic adenoma Iatrogenic/factitious (L-thyroxine, amiodarone, etc.) Transient hyperthyroidism Subacute and Hashimoto’s Rare causes: hypersecretion of TSH (e.g., pituitary neoplasms), struma ovarii, ingestion of large amounts of iodine in a patient with preexisting thyroid hyperplasia or adenoma (Jod-Basedow phenomenon), hydatid mole, carcinoma of thyroid, amiodarone
are mediated by increased Na/K pump activity and tend to be refractory to digoxin control) Download 3.95 Mb. Share with your friends:
|