Pathology- Endocrine

What is DM?
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Terms in this set (49)
What is DM?
- 'excessive sweet urine'
- group of diseases char by high blood glucose >126 fasting
- excessive thirst, freq urination, increased appetite
TYpe I DM
- Autoimmune destruction of B cells
- Insulin dependent, usually juvenile
- Genetic and environmental components
- Treat: Insulin
- 5-10% all diabetes cases
Type II DM
- 90-95% cases

- non-insulin dependent, usually adult onset
- Obesity aggravating, not causative

- Causes: Disorder of insulin receptor signaling, Impaired target tissue response to insulin (skeletal muscle, fat, liver), Impaired Beta-cell function
- Genetic, environmental components

- Treat: Diet, exercise, drugs, sometimes insulin
MODY- Maturity onset diabetes of the young
- monogenic single gene mutation disorders causing hyperglycemia of early onset
Gestational Diabetes
3-5% of pregnancies
- Placental hormones?
- Increases susceptibility to developing T II DM
- High birth weight in baby
(hyperglycemia --> Increases fetal growth)
2 Acute Diabetic Complications, warning signs
- Can be life threatening
1. Dehydration. Warning Signs: Excessive thirst, frequent urination.
(glycosuria--> increased urine volume)
2. Diabetic Ketoacidosis
Warning sign: fruity smell on breath. can cause coma, death.
(muscle fat can't pick up glucose, so fat mobilized. ketone bodies are b.d. prod o/ fatty acid metabolism)
5 Chronic Complications of Diabetes
- DM is a top contributor to death
1. Vascular Disease
2. Retinopathy
3. Neuropathy
4. Nephropathy
5. Insulin SHock?
Describe Vascular disease due to DM
- Microvascular disease --> 1.Atherosclerosis. DM makes this worse- inflammation, dyslipidemia- CVD major COD in diabetics.
2. Affects small vessels like capillaries
- Basement membrane thickening: deprives tissue of nutrients, impairs waste removal
- Microaneurysms, occlusion, leakage, hemorrhage: from Neovascularization! (weak abnormal vessels prone to rupture)
Mechanism of retinopathy in DM
- microvascular changes in retina and neurotixicity to neurons in retina, neovascularization
Mechanism of Nephropathy in DM
- Kidney failure
- #2 leading COD from DM
- microvascular changes
Mechanism of Neuropathy in DM- Microvascular changes, neurotoxicity 1. Peripheral: Most common. Evenly distributed. 50% diabetics have neuropathy . Numbness, tingling, pain. Poor wound healing, tissue damage, gangrene. 2. Autonomic: CV. Silent MI, GI, GU, ocular problems 3. Other types of Neuropathy: - Focal neuropathy: Certain nerve distributions. - Proximal - thighs, buttocks. - Localized- face, chest, foot.6 Mechanisms of Toxicity in DMIncreased Glucose causes: 1. AGEs - advanced glycation end products - accumulate, cause capillary basement membrane thickening, trigger inflammation 2. Alternate metabolic Pathways- inflammation 3. Excess glycolysis generates ROS 4. Changes in second messenger systems (PKC) 5. Decreased insulin and insulin-r cause: Changes in GF signaling (vascular endothelial cell GF) 6. Diversion of glucose into other metabolic pathways and excess glycolysis: neovascularizationInsulin shockVery high insulin leads to increased glucose uptake in fat and muscle- decreasing blood glucose- decreasing glucose to brain (b/c no insulin-r, not insulin-sensitive)- leading to confusion, coma, death Complication of DMAnatomy- Anterior Pituitary- Sits under hypothalamus in sella turcica - 1 cm in size - Optic chiasm just above - Cell types: Corticotrophs- ACTH Thryotrophs: TSH GOnadotrophs: FSH LH SOmatotrophs: GH Lactotrophs- ProlactinHormones of the Anterior Pituitary- ACTH: increases cortisol to withstand stress - TSH: increases thyroid hormones, BMR, growth - LH and FSH: sex steroids - GH: insulin-like GF- increases growth, glucose - PRL: Milk production, breast development3 Causes of Hyperpituitarism1. Most common: Hypersecreting adenomas 2. Hyperplasia: benign, non-neoplastic 3. Paraneoplastic syndromes: HOrmone secreting nonpituitary tumors like ACTH- eg lung tumor3 Causes of Hypopituitarism1. Damage from Tumor: Non secreting tumor grows in sella turcica, crushes sella/ pituitary 2. Ischemic injury 3. Damage from surgery, radiationPituitary Tumors1. Adenoma 2. Microadenoma 3. Hypersecreting 4. Silent 5. adenocarcinomasPituitary Adenoma- Bening, common, 1/4 developPituitary Microadenoma<1cm- size of gland itself (macro >1cm)Hypersecreting Pituitary tumorOverproduction of hormone causes effectsSilent Pituitary tumorDoesn't produce excess hormone, can't detect in blood. May be larger on detection because not caught until cognitive issues develop.Pituitary adenocarcinomaRare, not hypersecreting4 Mass effects of Pituitary tumor- Damage due to tumor bulk, displacement of structures 1. Pituitary damage produces Hypopituitary state 1. Sella Turcica erosion: break through sphenoid sinus. must be surgically repaired. 2. Bitemporal hemianopsia: Optic chiasm compression, tunnel vision 3. Pituitary Apoplexy: (apoplexy= stroke). Hemorrhage into adenoma- vasculature fragile, you have bleeding and expansion of mass- get HA, n/v, visual disturbances. Rare. life threatening.Prolactin Disorders- Hyperprolactinemia- Prolactin hypersecreting adenoma most common - Increased prolactin: Amenorrhea, Galactorrhea (inappropriate mild secretion) - Low libido, infertility - Caused by: Adenomas, Pituitary stalk trauma, drugs - Stalk interruption/compression syndrome: main negative control of prolactin from Hthal is DA. Stalk damage interrupts DA to pituitary, causes high prolactin. Any drugs that block dopamine-r can also cause these effects.2 Disorders of GH Excess1. Gigantism: Children. Increase in body size before puberty (especially height) 2. Acromegaly: Adults. GH secreting tumor in pituitary after puberty- long bones closed but face, skull, hands feet enlarge, soft tissue and tongue and heart enlarge. - Happens in middle age2 Disorders of GH Deficiency1. Pituitary Dwarfism: Children. Normal proportions but small. 2. Adult GH deficiency: Important for muscle mass. SIgns: weakness, fatigue, increased fat mass, decr muscle mass. Causes: radiation, trauma.1 Disorder of Posterior Pituitary Dysfunction1. Diabetes Insipidus - Insufficient ADH, excessive urine production - Tx: ADH nasal sprays - Etiology: Idiopathic, tumors, post-hypophysectomy, head traumaThyroid Goiter- Caused by excessive stim of TSH-r (by trophic hormone) - Nontoxic: low to normal thyroid hormones - Toxic: high thyroid hormoneHyperthyroidism- 2 results1. Thyrotoxicosis: hypermetabolic state due to high hormone levels. (increased HR< anxios, high metabolism, increased appetite, trouble sleeping) 2. Thyroid Storm: Abrupt onset of thyrotoxicosis, can be life threatening- leads to fatal cardiac arrhythmia, staring appearanceS/Sx of HyperthyroidismBMR increased: high appetite, heat intolerance Tachycardia, arrhythmias CNS tremor hyperactivity anxiety Ocular: staring appearance, eyelid retractionGrave's Disease- 80% Hyperthyroidism cases - Autoimmune disorder (antibody activates TSH-r, stimulating thyroid) - S/SX: TSH decrease, T4 increased, thyroid enlarges - Thyroid opthalmopathy: proprosis/ exophthalmos. (fibroblasts behind eyes expand)2 Hypothyroid Conditions1. Myxedema 2. CretinismMyxedema- from hypothyroidism - Decreased BMR- fatigue, cold intolerance - CNS signs: listless, mental sluggishness - Facial changes- edema, broadening of featuresCretinismChildren and babies from hypothyroid - Profound intellectual impairment , short stature (from GH lack)2 Causes of Hypothyroidism1. Iodine Deficiency: Rare in US 2. Hashimoto Thyroiditis: Autoimmune, gland destroyed- replaced by fibrosis. take thyroxine.Mild (subclinical) hypothyroidism- Normal thyroid hormones, high TSH - low BP, low HRThyroid TUmors -2- usually not functional 1. Adenomas: More common. Follicular epithelium 2. Adenocarcinomas: Major risk factor= ionizing radiation (x-rays). - Most have excellent prognosisFunction of Parathyroid hormoneRegulates calciumHyperparahyroidism1. Primary: Spontaneous overproduction PTH, hypercalcemia. 80% from adenoma. 2. Secondary: PTH overproduction from low blood Calcium 3. PTH buried in thyroid glandS/Sx- Hyperparathyroidism- Stones, Bones, Moans, Groans - Renal stones - Osteoperotic fx - CNS alterations: depression, seizures - GI disturbances: Gallstones, nausea, ulcersHypoparathyroidism- S/Sx1. Tetany: Muscle spasms due to low calcium. 2. Paresthesias: tingling 3. CNS effects- confusion, seizuresAdrenal Cortex hormones (3)- Cortisol - Aldosterone - DHEA (weak androgens)Adrenal Cortex disorders1. Addison disease 2. Cushing's disease 3. Congenital adrenal hyperplasiaAddison's Disease- Chronic Adrenal cortex insufficiency - Usually autoimmune - S/SX: Low plasma sodium (hyponatremia), fatigue, weakness, stress intolgerance, hyperpigmentation (especially in face- stim melanocytes) -Cushing SYndrome- Adrenal Cortex disordern, High levels of glucocorticoids - Cause of endogeneous types: 1. Corticortoph adenoma, adrenal tumor, hyperplasia 1. Pituitary corticotroph adenoma: Cushing disease 2. Paraneoplastic Cushing syndrome: ACTH producing tumor. 95% cases doctor induced by gluticocorticoid therapy for inflammatory condition. - ACTH low, adrenal cortex atrophies 3. Signs/ Symptoms: Cental obesity, buffalo hump, moon face- fat deposition in face, weakness and fatigue, osteoporosis, CNS effects- mod swings, depression. Adrenal atrophy or hyperplasia depending on cause.COngenital Adrenal HyperplasiaAdrenal cortex pathology - Etiology: Deficiency of hormone in steroid synthetic pathway- lack glucocorticoids, mineralcorticoids - High levels of androgens Signs/Sx: 1. Masculinization in children 2. Hirsuitism, Oligomenorrhea: women 3. Oligospermia: men (low sperm count)Adrenal Medulla HormonesEPI, NEAdrenal Medulla Pathology1. Pheochromocytoma: TUmor of chromaffin cells Hypersecreting epinephrine. - Signs: Hypertension, tachy, palpitations, headache, anxiety