Term
|
Definition
|
|
Term
| Alpha cells secrete what? |
|
Definition
|
|
Term
| Sigma cells secrete what? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What is the function of VIP? |
|
Definition
Increase GI fluid secretion
Increase glycogenolysis |
|
|
Term
| What is the estimated lifetime risk of diabetes? |
|
Definition
| 1 in 3 for males & 2 in 5 for females |
|
|
Term
| What are the general characteristics of the anterior lobe of the pituitary? |
|
Definition
Derived from Rathke’s pouch
Contains cells that secrete hormones that activate peripheral endocrine glands
Release of anterior pituitary hormones is regulated by hypothalamic releasing hormones
Hypothalamic releasing hormones are delivered to the anterior pituitary via the hypophysial portal circulation |
|
|
Term
| What are the general characteristics of the posterior lobe of the pituitary? |
|
Definition
Derived from an outpouching of the floor of the 3rd ventricle
Has a separate blood supply
Consists of modified glial cells & axons extending from the supraoptic & paraventricular nuclei in the hypothalamus
Neurons in the supraoptic & paraventricular nuclei produce ADH & oxytocin ADH & oxytocin are stored in axon terminals in the post lobe |
|
|
Term
| What are the five cells found in the adenohypophysis (anterior pituitary)? |
|
Definition
| Lactotrophs, Somatotrophs, Corticotrophs, Thyrotrophs, Gonadotrophs |
|
|
Term
| GnRH stimulates the release of what hormones in the adenohypophysis (anterior pituitary)? |
|
Definition
|
|
Term
| Dopamine inhibits the release of what? |
|
Definition
| Prolactin from the anterior pituitary |
|
|
Term
| What kind of visual field defects would you classically expect from a patient with a pituitary tumor? |
|
Definition
|
|
Term
| What is the most common cause of hyperpituitarism? |
|
Definition
| Functioning pituitary adenomas |
|
|
Term
| What is the most common cause of hyperpituitarism? |
|
Definition
| Prolactin secreting adenoma (prolactinoma) |
|
|
Term
| What is the preferred technique for diagnosing pituitary adenomas? |
|
Definition
|
|
Term
| What is diagnostic for a prolactinoma? |
|
Definition
| Serum prolactin level 200 ng/ml |
|
|
Term
| How do you treat a prolactinoma? |
|
Definition
Bromocriptine (dopamine receptor agonist)
surgery (transsphenoidal)
radiation |
|
|
Term
| How does hypothalamic disease cause hyperprolactinemia? |
|
Definition
| Normally secretes dopamine which inhibits prolactin |
|
|
Term
| What type of drugs might cause hyperprolactinemia? |
|
Definition
| Anti-dopaminergic drugs (e.g. phenothiazines, haloperidol) |
|
|
Term
| What are some uncommon causes of hyperprolactinemia? |
|
Definition
Estrogen therapy
Renal failure
Primary Hypothyroidism |
|
|
Term
| What are the symptoms of hyperprolactinemia? |
|
Definition
women: galactorrhea, amenorrhea, infertility, dec libido
men: dec libido, impotence, rarely galactorrhea & gynecomastia |
|
|
Term
| Why does estrogen cause hyperprolactinemia? |
|
Definition
| Upregulates prolactin gene |
|
|
Term
|
Definition
| Excess growth hormone in adults |
|
|
Term
| What are the characteristics of Acromegaly? Complications? |
|
Definition
| enlargement of the skull, facial bones, jaw, hands & feet overgrowth of soft tissues, visceromegaly, coarse facial features diabetes, hypertension, muscle weakness, arthritis, hypogonadism, cardiovascular disease |
|
|
Term
|
Definition
| Excess growth hormone in children before the closure of the epiphyses |
|
|
Term
| How are somatotroph adenomas diagnosed? |
|
Definition
Increased serum GH & IGF-1
serum prolactin may also be elevated
glucose suppression test
imaging scans (MRI better than CAT scan) |
|
|
Term
| Somatotroph adenomas are often associated with what gene expression? |
|
Definition
|
|
Term
| How does the gsp oncogene cause somatotroph adenomas? |
|
Definition
| A mutation in the alpha subunit that causes it to lose its GTPase activity. This results in persistent binding of GTP to the alpha subunit, which in turn results in constitutive activation of adenyl cyclase and unchecked proliferation of the somatotrophs |
|
|
Term
| What are corticotroph adenomas? |
|
Definition
| Basophilic microadenomas that secrete ACTH, causes Cushing disease |
|
|
Term
| How do you diagnose a corticotroph adenoma (ACTH secreting adenoma) |
|
Definition
Dexamethasone suppression test
ACTH be suppressed with a high dose |
|
|
Term
| What inflammatory disorders have the potential to cause hypothalamic lesions? |
|
Definition
|
|
Term
| What are causes of pituitary lesions? |
|
Definition
Tumors (esp. nonfunctioning adenomas)
Surgery or radiation
Inflammatory disorders and infections
Sheehan syndrome
Genetic defects (POU1F1) |
|
|
Term
| What are the effects of hypopituitarism? |
|
Definition
Children: dwarfism & infantilism
Adults: hypogonadism, hypothyroidism & hypoadrenalism |
|
|
Term
| Hypopituitarism accompanied by diabetes insipidus is almost always due to what? |
|
Definition
|
|
Term
| Mutations in POU1F1 result in what? |
|
Definition
| Encodes for pituitary specific transcription factor. Causes combined deficiencies of GH, prolactin, and TSH |
|
|
Term
| What causes Craniopharyngioma? |
|
Definition
Hypothalamic neoplasm derived from vestigial remnants of Rathke’s pouch
Benign, contains epithelial elements, often cystic with calcification |
|
|
Term
| What are the histological features of nonfunctioning pituitary adenomas? |
|
Definition
most consist of chromophobic cells or intensely eosinophilic cells (oncocytomas)
usually are sparsely granular
may stain negative for hormones with immunostains |
|
|
Term
| What is Sheehan Syndrome? |
|
Definition
Post-partum ischemic necrosis of the anterior pituitary
Precipitated by obstetric hemorrhage & shock causing destruction of the gland |
|
|
Term
| What are predisposing factors for Sheehan syndrome? |
|
Definition
anterior pituitary doubles in size during pregnancy
low pressure portal system unable to increase blood supply
abrupt onset of hypotension causes infarction |
|
|
Term
| What are the effects of Sheehan syndrome? |
|
Definition
| Failure of lactation, amenorrhea, hypothyroidism, hypoadrenalism & decreased skin pigmentation |
|
|
Term
| ADH deficiency is commonly known as what? |
|
Definition
|
|
Term
| What are the clinical features of Diabetes insipidus (ADH deficiency) |
|
Definition
urine of low specific gravity, inability to concentrate urine
polyuria, polydypsia and hypernatremia
caused by hypothalamic or pituitary lesions
some cases are idiopathic
usually corrected by drinking more H2O |
|
|
Term
| What causes Syndrome of Inappropriate ADH Secretion (SIADH)? |
|
Definition
| Ectopic ADH secretion by malignant neoplasms, most commonly due to small cell carcinoma of the lung |
|
|
Term
| What are the effects of inappropriate ADH secretion? |
|
Definition
Excessive reabsorption of free water
Oliguria, urine of high specific gravity, inability to dilute urine, and hyponatremia |
|
|
Term
| The thyroid develops from what? |
|
Definition
The primitive pharynx
Descends in the midline & assumes its final position in the anterior neck below the larynx
Can descend too far (substernal thyroid) or too high (lingual thyroid) |
|
|
Term
| What are the general effects of thyroid hormone? |
|
Definition
| Increases basal metabolic rate and heat production, protein catabolism, sympathetic activity |
|
|
Term
| What is the most common cause of hyperthyroidism? |
|
Definition
|
|
Term
| What cells secrete calcitonin |
|
Definition
|
|
Term
|
Definition
Dietary iodine deficiency or thyroid digenesis, defect in TH synthesis, TH resistance
Seen in children, is congenital |
|
|
Term
|
Definition
|
|
Term
| What is the most common cause of myxedema/hypothyroidism? |
|
Definition
|
|
Term
| What genes are associated with Hashimoto's thyroiditis? |
|
Definition
| Polymorphisms in CTLA4 and PTPN22 |
|
|
Term
| What causes Hashimoto's thyroiditis? |
|
Definition
Autoreactive helper T-cells enacting immune destruction
Targeted by B cells secreting antithyroid antibodies directed against thyroid peroxidase, TSH receptors, iodine transporters, etc.
Mediated by FasL binding to Fas signaling apoptosis |
|
|
Term
| What characteristic cells can be seen in Hashimoto's thyroiditis? |
|
Definition
| Hurthle cell metaplasia with infiltrates of lymphocytes and plasma cells |
|
|
Term
| What genes are associated with Grave's disease? |
|
Definition
| Polymorphisms in CTLA4 and PTPN22 |
|
|
Term
| What are the physical signs of Grave's disease? |
|
Definition
Symmetrical thyroid enlargement
Ophthalmopathy via expression of TSH-r in orbital firboblasts |
|
|
Term
| What causes Grave's disease? |
|
Definition
Helper T cells reacting to thyroid Ags
Causes B-cell clones that produce autoantibodies reactive with TSH receptors
Auto-abs act as TSH-r agonists, increases TH secretion |
|
|
Term
| How do you treat Grave's disease? |
|
Definition
| Beta-blockers, porpylthiouracil, ablation, etc. |
|
|
Term
| Toxic thyroid adenomas secrete what? |
|
Definition
|
|
Term
| What is the most common manifestation of thyroid disease? |
|
Definition
|
|
Term
| What causes the growth of goiters? |
|
Definition
Dec hormone synthesis causes inc TSH which induces hyperplasia and hypertrophy
Non-toxic/simple goiters are due to iodine deficiency or consumption of goitrogen foods. May sporadically occur due to hereditary defect in TH synthesis. Most are euthyroid |
|
|
Term
| What are the characteristics of multinodular goiters? |
|
Definition
Derived from diffuse goiters, can be monoclonal or polyclonal
Most are euthyroid T3/T4 normal, TSH high
Not in Graves, no ophthalmopathy or dermopathy
May grow 100x, compress trachea, vessels, etc |
|
|
Term
| What causes the symptoms of myxedema? |
|
Definition
| Accumulation of glycosaminoglycans |
|
|
Term
| What is the most common thyroid tumor? |
|
Definition
|
|
Term
| How do thyroid adenomas present? |
|
Definition
Can progress to carcinoma
Is usually a sharply demarcated solitary nodule with fibrous capsule
Most are nonfunctioning cold nodules |
|
|
Term
| What is the major risk factor for the development of thyroid cancer? |
|
Definition
|
|
Term
| What is the most common thyroid cancer? |
|
Definition
|
|
Term
| Papillary carcinoma is associated with what genetic anomalies? |
|
Definition
Majority are due to a gain of function mutation in the BRAF gene
Associated with the ReT/PTC oncogene due to rearrangement in chromosome 10 |
|
|
Term
| What is the characteristic appearance of papillary carcinomas? |
|
Definition
Unencapsulated
Diagnostic Orphan Annie Eye and Psammoma bodies |
|
|
Term
| What is medullary carcinoma? |
|
Definition
| Neuroendocrine tumor of C cells that secretes calcitonin |
|
|
Term
| What genetic anomalies are associated with medullary carcinoma? |
|
Definition
Can be sporadic or familial, associated with MEN-2A, MEN-2B or FMTC
Associated with activating mutation in the RET protooncogene |
|
|
Term
| What is the difference in the presentation of sporadic and familial medullary carcinoma? |
|
Definition
| Sporadic only affects one lob, familial is bilateral |
|
|
Term
| How do medullary carcinoma cells present? |
|
Definition
Cells show amyloid deposits in the stroma, positive for calcitonin and ghromagranin
Histologically important nests and trabeculae |
|
|
Term
| What is anaplastic carcinoma? |
|
Definition
| Undifferentiated tumors derived from thyroid follicular epithelium |
|
|
Term
| What are the characteristics of anaplastic carcinoma? |
|
Definition
Most common in elderly, poor prognosis
May exhibit giant cell and spindle cell types, widely invasive and metastatic |
|
|
Term
| Chief cells in the parathyroid may become overused and transition to what form? |
|
Definition
| Oxyphil cells that are burnt out and water clear cells with glycogen |
|
|
Term
| What is primary hyperparathyroidism? |
|
Definition
| Autonomous hypersecretion of PTH, accounts for 90% of hypercalcemia cases |
|
|
Term
| Primary hyperparathyroidism is more common in women and prevalent among which MEN groups? |
|
Definition
|
|
Term
| What are some complications of hyperparathyroidism? |
|
Definition
| osteitis fibrosa cystica, nephrolithiasis, metastatic calcification, pancreatitis |
|
|
Term
| What is the most common cause of primary hyperparathyroidism? |
|
Definition
|
|
Term
| What causes parathyroid adenomas? |
|
Definition
Caused by overexpression of cyclin D1
Associated with MEN1, usually solitary and encapsulated |
|
|
Term
| What is required to make a diagnosis of parathyroid carcinoma? |
|
Definition
| Presence of invasion or metastases |
|
|
Term
| What is osteitis fibrosa cystica? |
|
Definition
Symptomatic condition of hyperparathyroidism
Characterized by inc bone resorption causes bone pain, cystic spaces in bone, “brown tumors” |
|
|
Term
| What is secondary hyperparathyroidism? |
|
Definition
Compensatory hypersecretion of PTH caused by hypocalcemia
Labs show inc PTH and phosphate, low/dec Ca++ |
|
|
Term
| What is the most common cause of secondary hyperparathyroidism? |
|
Definition
| Chronic renal failure and vit D deficiency |
|
|
Term
| What is tertiary hyperparathyroidism? |
|
Definition
| Occurs with long standing secondary hyperparathyroidism due to chronic renal failure. Over time, the parathyroid becomes autonomous and continually secretes PTH |
|
|
Term
| What causes autosomal dominant hypoparathyroidism |
|
Definition
| Gain of function mutation in the VASR gene, known as DiGeorge syndrome |
|
|
Term
| What complications can arise from hypoparathyroidism? |
|
Definition
| Tetany, seizures, prolonged QT, cataracts, parkinsonism |
|
|
Term
| What is pseudohypoparathyroidism? |
|
Definition
| Hypocalcermia and hyperphosphatemia but with increased PTH and parathyroid hyperplasia. Caused by end organ resistance to PTH due to kidneys and bone not responding |
|
|
Term
| What causes pseudohypoparathyroidism type IA? |
|
Definition
Decreased cAMP response to PTH
Known as Albright hereditary osteodystrophy
Causes short metacarpals, metatarsals, short stature |
|
|
Term
| What causes pseudohypoparathyroidism type IB? |
|
Definition
Normal cAMP response to PTH but with decreased response to cAMP
Causes short metacarpals, metatarsals, short stature |
|
|
Term
| What are the different zones of the adrenal gland and what do they secrete? |
|
Definition
GFR = Glomerulosa, Fasciulara, Reticularis
Salt Sweet Sex = aldosterone, cortisol, androgens |
|
|
Term
| Cortisol is often colloquially referred to as what? |
|
Definition
|
|
Term
| What is Waterhouse-Friderichsen Syndrome? |
|
Definition
Sudden withdrawal of long term corticosteroid therapy
Induces hypoadrenalism |
|
|
Term
| What is Cushing Syndrome? |
|
Definition
| Any condition that has elevated glucocorticoid levels, usually cortisol |
|
|
Term
| What is the most common cause of Cushing syndrome? |
|
Definition
| Exogenous administration of cortisol |
|
|
Term
|
Definition
| Pituitary hypersecretion of ACTH which causes Cushing Syndrome |
|
|
Term
| What are the visual indicators of Cushing disease? |
|
Definition
| Hyperpigmentation of the skin, adrenals are bilaterally hyperplastic |
|
|
Term
| Ectopic secretions of CRH or ACTH is usually due to what? |
|
Definition
| Small cell carcinoma of the lung |
|
|
Term
| What is Primary Hyperaldosteronism? |
|
Definition
Autonomous hypersecretion of aldosterone, suppresses the renin-angiotensin system
Labs show inc aldosterone/renin ratio, dec or normal K+, hypertension |
|
|
Term
| What causes bilateral idiopathic hyperaldosteronism |
|
Definition
| Overexpression of aldosterone synthase gene |
|
|
Term
| What causes clucocorticoid-remediable hyperaldosteronism |
|
Definition
Fusion of aldosterone synthase on 11beta-hydroxylase genes
Results in adrenocorticoid cells secreting hybrid steroids as well as cortisol and aldosterone |
|
|
Term
| 11-hydroxylase Deficiency causes what? |
|
Definition
Hyper aldosterone and androgen production
No cortisol is produced |
|
|
Term
| 17-hydroxylase Deficiency causes what? |
|
Definition
Hyper aldosterone production only
No cortisol is produced |
|
|
Term
| 21-hydroxylase Deficiency causes what? |
|
Definition
Hyper androgen production only
No cortisol is produced |
|
|
Term
| What causes congenital adrenal hyperplasia? |
|
Definition
Defect most commonly in 21-hydroxylase, causes dec cortisol, defective ACTH feedback, increased ACTH leading to bilateral adrenocortical hyperplasia
Leads to lack of aldosterone or cortisol production, causes salt wasting |
|
|
Term
| What is the characteristic clinical feature of acute adrenal insufficiency (aka Waterhouse-Friderichsen syndrome) |
|
Definition
| Meningococcal septicemia with widespread purpura |
|
|
Term
| What causes acute adrenal insufficiency? |
|
Definition
| Massive bilateral adrenal hemorrhage causing rapid hypotensive shock |
|
|
Term
| Primary chronic adrenal insufficiency is also known as what? |
|
Definition
|
|
Term
| What causes Addison's disease? |
|
Definition
| 90% destruction of the adrenal cortex, may be autoimmune, due to cancer or disease |
|
|
Term
| What are the effects of Addison's disease? |
|
Definition
Decreased cortisol and aldosterone cause salt wasting, hypoglycemia, low BP
Increased ACTH causes skin hyperpigmentation |
|
|
Term
| What causes secondary chronic adrenal insufficiency? |
|
Definition
Hypothalamic pituitary lesion results in dec ACTH causes bilateral cortical atrophy
Zona Glomerulosa spared, does not respond to ACTH, aldosterone is normal |
|
|
Term
| What do chromaffin cells in the adrenal medulla secrete? |
|
Definition
| The catecholamines epinephrine and norepinephrine |
|
|
Term
| What is pheochromocytoma? |
|
Definition
| A neoplasm composed of chromaffin cells that secrete catecholamines, causes HTN |
|
|
Term
| Why is pheochromocytoma referred to as the "10% tumor"? |
|
Definition
10 % extra-adrenal (90% in medulla)
10 % bilateral in sporadic cases, but up to 50% are bilateral in familial cases
10 % in children
10 % are malignant in adrenal cases, but up to 40% are malignant in extra-adrenal cases |
|
|
Term
| Familial pheochromocytoma is associated with what? |
|
Definition
|
|
Term
| What is the characteristic feature of pheochromocytoma? |
|
Definition
| Paroxysmal hypertension related to catecholamine release, preceded by sense of apprehension |
|
|
Term
| How is pheochromocytoma diagnosed? |
|
Definition
| 24hr urine for catecholamines and metanephrines |
|
|
Term
| How do pheochromocytoma cells appear upon inspection? |
|
Definition
| Classic “zellballen” growth pattern where tumor cells are arranged into round nests surrounded by fibrovascular tissue traveculae |
|
|
Term
| What causes Multiple Endocrine Neoplasia 1? |
|
Definition
| Inherited germ-line mutations in tumor suppressor gene MEN-1 |
|
|
Term
| What are the symptoms of Multiple Endocrine Neoplasia 1 (MEN-1)? |
|
Definition
The “Three Ps”:
Parathyroid hyperplasia
Pancreatic Islet cell tumors causing gastrinomas, insulinomas, and VIPomas
Pituitary adenoma, most commonly prolactinoma |
|
|
Term
| What causes Multiple Endocrine Neoplasia 2A? |
|
Definition
| Inherited germ line mutation in the RET proto-oncogene |
|
|
Term
| What are the symptoms of Multiple Endocrine Neoplasia 2A (MEN-2A)? |
|
Definition
C cell hyperplasia and medullary thyroid carcinoma
Pheochromocytoma and parathyroid hyperplasia |
|
|
Term
| What is the difference between MEN-2A and MEN-2B? |
|
Definition
MEN-2B is more aggressive
Causes C cell hyperplasia, medullary thyroid carcinoma, pehochromocytoma as well as ganglioneuroma and marfanoid body habitus |
|
|
Term
| Familial Medullary Thyroid Cancer is a variant of what? |
|
Definition
|
|
Term
| How is Diabetes Mellitus diagnosed? |
|
Definition
Random glucose >200mg/dl with classic signs/symptoms
Fasting glucose >126mg/dl on more than one occasion
Abnormal glucose tolerance test >200mg/dl 2hrs after carb load |
|
|
Term
| What is the most important stimulus for insulin synthesis? |
|
Definition
|
|
Term
| Insulin uses which signalling pathway? |
|
Definition
| MAP kinase and PI-3K signaling pathway |
|
|
Term
| What is the most important metabolic function of insulin? |
|
Definition
| Insertion of GLUT-4 into cell membranes to enhance the transport of glucose into the cell |
|
|
Term
| What genes play the most important role in the susceptibility of diabetes mellitus? |
|
Definition
|
|
Term
| What is the major metabolic complication of type I diabetes? |
|
Definition
|
|
Term
| What causes type I diabetes? |
|
Definition
| Occurs after 90% of pancreatic beta cells have been destroyed |
|
|
Term
| What is the most important event in the pathogenesis of type II diabetes? |
|
Definition
| The development of decreased responsiveness of the target cells to insulin |
|
|
Term
| How does obesity facilitate insulin resistance in type II diabetes? |
|
Definition
Inc FFAs interfere with normal insulin signaling
Alters pattern of adipokine secretion to promote insulin resistance |
|
|
Term
| How does type II diabetes progress? |
|
Definition
| Early stages show hyperinsulinemia as beta-cells compensate to the insulin resistance. Continued demand causes Beta cells to begin to fail |
|
|
Term
| What factors contribute to susceptibility of beta cell failure in type II diabetes? |
|
Definition
| Genetics, apoptosis, amyloidosis, FFAs |
|
|
Term
| What characterized Maturity-Onset Diabetes of the Young (MODY)? |
|
Definition
Autosomal Dominant
Onset before 25, has impaired B cell function, no insulin resistance |
|
|
Term
| What are the different types of Maturity-Onset Diabetes of the Young (MODY)? |
|
Definition
Type 1 = HNF-4alpha mutation causes B-cell secretory defect
Type 2 = Glucokinase mutation causes mild B-cell secretory defect
Type 3 = HNF-1alpha mutation causes B-cell secretory defect
Type 4 = Insulin Promoter Factor-1 (IPF-1) mutation**
Type 5 = HNF-1beta mutation causes B-cell secretory defect
Type 6 = Neuro D1 mutation** |
|
|
Term
| Which types of MODY did Tommlinson highlight in class? |
|
Definition
Type 4 = Insulin Promoter Factor-1 (IPF-1) mutation**
Type 6 = Neuro D1 mutation** |
|
|
Term
| What causes Advanced Glycosylation End Products (AGEs)? |
|
Definition
A complication of diabetes
Plasma proteins induce cross-linking of type IV collagen by binding to basement membranes modified by AGEs
Causes trapping of LDL particles in artery walls
oAGEs bind to receptor RAGE to cause endothelial dysfunction, cytokine and growth factor release, ECM production, and vascular smooth muscle proliferation |
|
|
Term
| Why is the activation of protein kinase C a problem with diabetes? |
|
Definition
Hyperglycemia increases glucose within cells not requiring insulin for glucose transport, causes activation of PKC
Leads to inc VEGF and pro-inflammatory cytokines by endothelial cells |
|
|
Term
| How does diabetes induce oxidative cellular damage? |
|
Definition
| Causes hyperglycemia. Glucose is converted by aldose reductase to sorbitol, requiring NADPH. Drop in NADPH causes oxidative cell damage |
|
|
Term
| What glomerular abnormality is pathognomonic for diabetes? |
|
Definition
Nodular Glomerulosclerosis (Kimmelstiel-Wilson Disease)
Associated with chronic renal failure |
|
|
Term
| What is the most common type of Pancreatic Endocrine Neoplasms (Islet Cell Tumors) |
|
Definition
Insulinomas
Majority are benign |
|
|
Term
| Which types of pancreatic endocrine neoplasms are associated with functional tumors |
|
Definition
| Hyperinsulinism, Zollinger-Ellison Syndrome, and MEN-1 |
|
|
Term
| Zollinger-Ellison Syndrome is caused by what? |
|
Definition
|
|
Term
| Necrolytic migratory erythema is caused by what? |
|
Definition
|
|
Term
| Somatostatinoma can cause what? |
|
Definition
|
|
Term
|
Definition
| Increased BUN and Creatinine due to decreased GFR |
|
|
Term
| What is prerenal azotemia? |
|
Definition
| Hypoperfusion of the kidneys causing impaired renal function but without any parenchymal damage |
|
|
Term
| What is postrenal azotemia? |
|
Definition
| Caused by obstruction of urine flow below the level of the kidneys |
|
|
Term
|
Definition
| Azotemia combined with clinical manifestations such as hyperparathyroidism, pericarditis, is associated with renal failure |
|
|
Term
| Diminishing renal reserve is defined as what? |
|
Definition
|
|
Term
| Renal insufficiency is defined as what? |
|
Definition
|
|
Term
| Chronic renal failure is defined as what? |
|
Definition
|
|
Term
| End stage renal disease is defined as what? |
|
Definition
| GFR >5% of normal, terminal stage of uremia |
|
|
Term
| What is the function of the glomerular basement membrane? |
|
Definition
| Negative charge excludes albumin |
|
|
Term
| What is Primary glomerulopathy? |
|
Definition
| Glomeruli injured, kidney is the only organ involved |
|
|
Term
| What is Secondary glomerulopathy? |
|
Definition
| Glomeruli is injured due to systemic disease |
|
|
Term
|
Definition
|
|
Term
|
Definition
| only a certain proportion of glomeruli involved |
|
|
Term
|
Definition
| Entire glomerulus involved |
|
|
Term
|
Definition
| only part of glomerulus involved |
|
|
Term
| What are the characteristics of acute nephritic syndrome? |
|
Definition
| Hematuria, azotemia, variable proteinuria |
|
|
Term
| What characterizes nephrotic syndrome? |
|
Definition
| >3.5g proteinuria due to inc permeability, hypoalbuminemia, hyperlipidemia, lipiduria |
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Term
| What is the most common cause of nephrotic syndrome? |
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Definition
Minimal change disease
Also caused by focal segmental glomerulosclerosis, membranous glomerulopathy, and seen in systemic diseases diabetes mellitus, amyloidosis, SLE |
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Term
| What characterizes rapidly progressing glormerulonephritis |
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Definition
| Nephritis, proteinuria, acute renal failure |
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Term
| Which glomerulonephropathy does not cause nephritic syndrome? |
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Definition
|
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Term
| What is the major constituent of the slit diaphragm? |
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Definition
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Term
| How does does Goodpasture's Syndrome cause glomerulonephropathy? |
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Definition
| An autoantibody from the lungs is directed against glomerular basement membrane |
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Term
|
Definition
| A membrane attack complex that lyses glomerular cells and acts as mediators that activate mesengial cells for the release of oxidants and proteases |
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Term
| What is notable about Antibody Dependent Cell Mediated Cytotoxicity (ADCC)? |
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Definition
| Injures glomerular cells WITHOUT activating the complement cascade |
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Term
| What happens when GFR drops to 30-50% of normal? |
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Definition
| Invariably progresses to end stage renal disease at a constant rate |
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Term
| What are the 2 major characteristics of progressive renal disease? |
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Definition
Focal segmental glomerulosclerosis
Tubulointerstitial damage causing fibrosis causing a decrease in renal function
Proteinuria plays major role in renal damage |
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Term
| What is the likely cause of proteinuria? |
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Definition
| Injury to visceral epithelial cells (podocytes) |
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Term
| What causes Acute Proliferative Glomerulonephritis? |
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Definition
Diffuse proliferation of glomerular cells with an influx of leukocytes caused by a deposition of immune complexes
May be exogenous due to infection or endogenous as in SLE |
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Term
| What are the characteristics of post-streptococcal glomerulonephritis? |
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Definition
1-3 wks following a group A beta-hemolytic strep pharyngeal or skin infection
Most frequent in children, caused by immune complex deposition
Exhibits compression of glomerular capillary **lumina, deposits of IgG, IgM, and C3 along the basement membrane, and electron dense deposits seen as humps
Has red cell casts and periorbital edema |
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Term
| What are the characteristics of Rapidly Progressive/Crescentic Glomerulonephritis |
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Definition
Rapid loss of renal function, severe oliguria, death from renal failure in if untreated
Crescent formation by proliferative parietal cells and infiltrates in bowman’s space
Electrom micrograph shows focal ruptures in the glomerular basement membrane*
Presents with a cute nephritic syndrome |
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Term
| What are the characteristics of Type I RPGN? |
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Definition
Linear deposits of Ig’s and C3, renal function limited
Some have cross reactivity with alveolar capillary basement membranes, causing Goodpasture syndrome
Treated with plasmapheresis |
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Term
| What are the characteristics of Type II RPGN? |
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Definition
Immune complex mediated, granular staining for Ig’s and C3
Not helped by plasmapheresis
Associated with postinfection glomerulonephritis, lupus nephritis, Henoch-Schonlein purpura |
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Term
| What are the characteristics of Type III RPGN? |
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Definition
“Pauci-immune type” due to lack of Ig or C3
Most of ANCA, some helped with plasmapheresis but not all
Associated with Wegener granulomatosis and microscopic polyangiitis |
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Term
| What is responsible for membranous glomerulonephropathy? |
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Definition
C5b-C9 complex causes proteinuria, damage to visceral epithelial cell membranes
Activates mesengial cells to release proteases and oxidants that damage glomerular capillary walls |
|
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Term
| What is characteristic of membranous glomerulonephropathy? |
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Definition
Spikes on silver stains, subepithelial deposits on EM, diffuse thickening of the glomerular capillary wall, glomerular deposits
Usually presents with nephrotic syndrome |
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|
Term
| What is the most common cause of nephrotic syndrome in children? |
|
Definition
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|
Term
| What are the characteristics of minimal change disease? |
|
Definition
Sometimes follows respiratory infection, vaccination, or Hodgkin’s disease
Electron micrograph shows diffuse loss of foot processes on visceral epithelium. However, glomerulus apears normal under light microscopy
Proximal tubular cells are laden with lipid
Responds dramatically to corticosteroids |
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Term
| What is the most common cause of nephrotic syndrome in adults? |
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Definition
| Focal Segmental Glomerulosclerosis (FSGS) |
|
|
Term
| What are common secondary causes of focal segmental glomerulosclerosis? |
|
Definition
HIV infection and heroin addiction
HIV cases show collapsing glomerulopathy |
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|
Term
| What is the clinical hallmark of focal segmental glomerulosclerosis? |
|
Definition
Epithelial damage caused by circulating cytokines
Also shows diffuse loss of foot process, focal detachment of podocytes, can progress to ESRD |
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Term
| Membranoproliferative Glomerulonephritis (MPGN) often presents with what? |
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Definition
| Seen in combined nephritic/nephrotic patient |
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Term
| What is diagnostically characteristic of membranoproliferative glomerulonephritis (MPGN)? |
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Definition
| Double Countor glomerular capillary wall has tram track appearance due to duplication of the glomerular basement membrane with interposition of mesengial cell processes |
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Term
| What is distinct about type I membranoproliferative glomerulonephritis (MPGN) |
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Definition
*Subendothelial electron dense deposits
Deposition of immune complexes with both classical and alternative pathways |
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Term
| What is distinct about type II membranoproliferative glomerulonephritis (MPGN) |
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Definition
Lamina densa electron dense deposits
Mesangial rings due to C3 but other immune complexes usually absent
C3NeF stabilizes alternative pathway C3 convertase, initiates injury |
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Term
| What would you see secondary MPGN? |
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Definition
| Chronic immune complex disorders such as SLE |
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|
Term
| What is the most common glomerulonephropathy in the world? |
|
Definition
| IgA Nephropathy/Berger Disease |
|
|
Term
| What causes IgA nephropathy/Berger disease? |
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Definition
Prominent IgA deposits in the mesangium, variable appearance
Due to increased mucosal IgA synthesis in response to Ag’s in the respiratory tract of GI
AgA1 complexes are entrapped in the mesangium
Insidious development, slow progression to uremia and death |
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Term
| What is the most common cause of autosomal dominant (adult) polycystic kidney disease? |
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Definition
PKD1 encodes for polycystin 1
Polycystin forms complex in cilia that regulates influx of Ca++, mutation increases intracellular Ca++, causing cyst formation |
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Term
| How does autosomal dominant (adult) polycystic kidney disease present? |
|
Definition
Kidneys bilaterally enlarged with functioning nephrons in between numerous cysts
Can be asymptomatic for years, many also have liver cysts |
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Term
| What causes Autosomal Recessive (childhood) Polycystic Kidney Disease? |
|
Definition
| Involves PKHD1 gene that encodes fibrocystin, a cell surface receptor with a role in collecting duct and biliary duct differentiation |
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Term
| How does Autosomal Recessive (childhood) Polycystic Kidney Disease present? |
|
Definition
| Causes numerous small cysts in cortex and medulla, cylindrical dilation of all collecting ducts, potential congenital hepatic fibrosis causing portal hypertension |
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|
Term
| What is characteristic of Nephronopthisis? |
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Definition
| Cysts are in the medulla, is autosomal recessive or sporadic, seen in younger |
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|
Term
| What causes adult-onset medullary cystic kidney disease? |
|
Definition
| Associated with genes MCKD1 and MCKD2 |
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Term
| What is characteristic of adult-onset medullary cystic kidney disease? |
|
Definition
| Cysts form in the medulla at the cortico-medullary junction causing chronic tubulointerstitial nephritis |
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|
Term
| How are urinary tract obstructions diagnosed? |
|
Definition
| Ultrasound or intravenous pyelography |
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|
Term
| What is diagnostic for drug induced interstitial nephritis? |
|
Definition
Biopsy shows interstitial infiltration by mononuclear cells, particularly eosinophils
Drug binds to tubular cells causing IgE and cell mediated immune reaction |
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Term
| What causes analgesic nephropathy? |
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Definition
| Chronic tubulointerstitial nephritis with papillary necrosis caused by excessive intake of phenacetin-containing analgesics such as aspirin or aceteminophen |
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|
Term
| How is analgesic nephropathy diagnosed? |
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Definition
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Term
| Analgesic nephropathy increases the risk of what? |
|
Definition
| Transitional cell carcinoma |
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|
Term
| What causes acute uric acid nephropathy? |
|
Definition
| Precipitation of uric acid crystals in the renal tubules causing renal failure, most often seen with cancer chemotherapy |
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Term
| What is the most common cause of multiple myeloma (cancer of plasma cells)? |
|
Definition
Bence Jones Proteinuria
Bence Jones proteins combine with Tamm-Horsfall protein to form tubular casts
Can also be caused by amyloidosis and light chain deposit disease |
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Term
| Leukocyte Casts are diagnostic for what? |
|
Definition
|
|
Term
| The most important factor in urolithiasis stone formation is what? |
|
Definition
|
|
Term
| What is the most common cause of urolithiasis? |
|
Definition
|
|
Term
| Calcium oxalate stones are associated with what pathologies? |
|
Definition
Hyperparathyroidism, hypercalciuria, hyperuricosuria
Vegetarians at higher risk |
|
|
Term
| Magnesium ammonium phosphate stones cause what? |
|
Definition
|
|
Term
| Magnesium ammonium phosphate stones are associated with what pathogens? |
|
Definition
|
|
Term
| Uric acid stones caused by gout, leukemias, lymphomas require what for formation? |
|
Definition
|
|
Term
| Cystine stones are due to what? |
|
Definition
| Defects in the reabsorption of amino acids |
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|
Term
| What are the important features of renal papillary adenomas? |
|
Definition
Small benign well demarcated tumors
Do not differ histologically from papillary renal cell carcinoma, all regarded as potentially malignant |
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|
Term
| What is the most common renal cell cancer? |
|
Definition
|
|
Term
| What is the most prominent risk factor for renal cell carcinoma? |
|
Definition
|
|
Term
| What is the most common renal cell carcinoma? |
|
Definition
|
|
Term
| Clear cell carcinoma is caused by a loss of what gene? |
|
Definition
|
|
Term
| What causes renal papillary carcinoma? |
|
Definition
Multifocal origin:
Trisomies 7, 16, 18
Losss of Y chromosome in males
Familial caused by MET protooncogene on chromosome 7 |
|
|
Term
| What is characteristic of Chromophobe Renal Carcinoma? |
|
Definition
Sheets of cells showing pale eosinophilic cytoplasm and perinuclear halos
Forms from intercalated cells of collecting ducts
Connected with extreme hypodiploidy |
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|
Term
| How does interstitial cystitis present? |
|
Definition
Commonly seen in women, cystoscopy reveals fissures with punctate hemorrhages
Mast cells are prominent, bacterial infection is absent, cause may be autoimmune |
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|
Term
| What is diagnostic of Malacoplakia? |
|
Definition
| Sheets of macrophages containing phagosomes with bacterial debris, called Michaelis Gutmann bodies |
|
|
Term
| What causes malacoplakia? |
|
Definition
Higher in immunosuppressed transplant patients
Associated with E. coli and Proteus infections |
|
|
Term
| Urethritis is often accompanied by what other disease? |
|
Definition
| Cystitis in women and prostatitis in men |
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|
Term
| What is a urethral carbuncle? |
|
Definition
| Most common lesion of female urethra composed of inflamed highly vascular fibroblastic tissue, is surgically excised, quite common |
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Term
| Squamous transitional cell papillomas with inverterted papillomas and condylomas is characteristic of what? |
|
Definition
| Benign Urethral Epithelial Tumors |
|
|
Term
| Carcinomas from the posterior urethra are most commonly what? |
|
Definition
| Transitional cell carcinomas |
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|
Term
| Carcinomas from the anterior urethra are most commonly what? |
|
Definition
|
|
Term
| What is the most common renal tumor in children? |
|
Definition
| Wilms Tumor (Nephroblastoma) |
|
|
Term
| The majority of Wilms tumors are caused by what? |
|
Definition
| Sporadic, usually unilateral |
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|
Term
| What kind of characteristic growth pattern do you see in Wilms tumors? |
|
Definition
| Blastema, mesenchymal stroma & epithelial elements |
|
|
Term
| What syndromes increase the risk of Wilms tumor? |
|
Definition
| WAGR syndrome, Denys-Drash syndrome, Beckwith-Wiedemann syndrome |
|
|
Term
| Mutation of what genes can lead to Wilms tumor? |
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Definition
|
|
Term
| What causes anirida (WAGR syndrome) |
|
Definition
|
|
Term
| What is the most common cause of bladder tumors? |
|
Definition
Urothelial (Transitional Cell) Tumors
More common in males |
|
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Term
| What are risk factors for Urothelial (Transitional Cell) Tumors of the bladder? |
|
Definition
Cigarette smoking
Exposure to arylamines (esp. 2-naphthylamine)
Schistosoma haematobium infection (~ 70% of the tumors are squamous)
Analgesic abuse
Cyclophosphamide exposure
Bladder irradiation |
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|
Term
| Which type of urothelial (transitional cell) bladder tumors are the most invasive? |
|
Definition
| Flat urothelial carcinoma |
|
|
Term
| How are Urothelial (Transitional Cell) Tumors of the Urinary Bladder diagnosed? |
|
Definition
Cystoscopy with biopsy
Urine cytology
Flow cytometry
Fluorescent in situ hybridization |
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|
Term
| How are transitional cell carcinomas graded from least invasive to most invasive? |
|
Definition
Urothelial papilloma
PUNLMP
Papillary urothelial carcinoma low grade
Papillary urothelial carcinoma high grade |
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