Flashcards
Pathology 2 - Endocrine
Flashcards do conjunto (78)
- 1What are the risks associated with prediabetes?25% will develop overt diabetes within 5 years
Increased risk of CV disease - 2Which type of diabetes is more common?Type 2 (90-95%)
- 3What are the effects of insulin on peripheral tissues?
- 4In what patients does type 1 DM most commonly occur?children
- 5In what patients does type 2 DM most commonly occur?most commonly adult onset
but prevalence in children is increasing due to increased prevalence of childhood obesity - 6Describe the etiology/pathogenesis of type 1 diabetesEtiology:
1. Genetic predisposition
- polymorphisms in:
- HLAD3/D4
- insulin gene --> decreased expression in thymus --> escape of self-reactive T cells
- CTLA-4, PTPN2 --> normally inhibit T cell function
2. Environmental
- viral infections (mumps, rubella, Coxsackievirus)
LEADS TO:
loss of self-tolerance towards B-cell antigens --> production of Ab --> destruction of B-cells - 7Describe the stages of development of DM1genetic predisposition + normal B cell mass --> inciting event (ex. viral infection) --> autoimmune destruction of pancreas and progressive loss of B-cells --> eventually enough B-cells are damaged and overt diabetes manifests with deranged glucose metabolism
- 8Describe the etiology/pathogenesis of DM type 2obesity --> insulin resistance --> compensation via hyperinsulinemia --> B-cell dysfunction and insulin deficiency
- 9How does obesity contribute to insulin resistance? How does insulin resistance manifest in the various tissues?1. FFAs --> increased triglycerides within muscle and liver --> inhibition of insulin signaling
2. Adipokines released from adipose tissue --> promote hyperglycemia
3. FFAs lead to the release of proinflammatory cytokines --> promotes insulin resistance
Liver - failure to inhibit gluconeogenesis
Muscle - decreased uptake of glucose --> increased serum glucose
Adipose - failure to inhibit hormone-sensitive lipase --> high FFAs
- 10What are the monogenic forms of diabetes? What types of gene mutations are involved?1. Congenital Early Onset (neonatal)
- insulin gene
- mitochondrial DNA
- insulin receptor (synthesis, binding of insulin, signaling)
2. MODY (maturity-onset diabetes of the young - before 25y/o)
- genes involved with B-cell function - 11What are the risks for the fetus in gestational diabetes?congenital defects, stillbirth, overgrowth (macrosomia) due to increased IGFs stimulated by maternal hyperglycemia
- 12What are the causes of diabetes?
- 13What is the classic triad of diabetes? Describe the pathogenesis of eachpolyphagia, polyuria and polydipsia
Polyuria: hyperglycemia exceeds renal threshold for glucose reabsorption --> glucosuria --> osmotic diuresis
Polydipsia: renal water loss + hyperosmolality due to serum glucose stimulates osmoreceptors in brain
Polyphagia: catabolism of proteins and fats leads to increased appetite; is still associated with weight loss - 14Describe the pathogenesis of diabetic ketoacidosisabsolute insulin deficiency --> activation of hormone-sensitive lipase --> increase FFAs --> oxidation in liver to ketones --> ketonemia and ketonuria
ketonemia decreases blood pH --> metabolic acidosis - 15Describe the pathogenesis of nonketotic hyperosmolar comatype 2 diabetes mainly
polyuria leads to severe dehydration --> hyperglycemia
generation of ketone bodies is minimal due to low level of insulin production
most commonly seen in the elderly and disabled patients; symptoms are generally noticed very late - 16What are the main acute complications of diabetes mellitus?ketoacidosis
nonketotic hyperosmolar coma - 17What are the chronic complications of diabetes?Macrovascular disease --> accelerated atherosclerosis; increased MI, stoke, lower extremity ischemia
Microvascular disease (microangiopathy) --> retinopathy, nephropathy, neuropathy caused by diffuse thickening of BM (collagen 4)
Increased susceptibility to infections of skin, TB, pneumonia, and pyelonephritis - 18Describe how hyperglycemia contributes to the pathogenesis of diabetic macro and microvascular disease1. formation of AGE --> induce release of cytokines, ROS, procoagulant activity, proliferation of vascular SM, cross linking of LDL --> atherosclerosis
2. activation protein kinase C --> production of VEGF
3. glucose converted to sorbitol by aldose reductase in some tissues --> NADPH and used up and not available for GSH which increases oxidative stress - 19Describe the morphology of the pancreas in type 1 and 2 DMType 1:
- reduction in number and size of islets
- leukocytic infiltrates
Type 2:
- amyloid deposition between and within capillaries, between cells
- fibrosis - 20What is the most common cause of death in diabetics?myocardial infarction
- 21Describe the features of diabetic nephropathy1. Glomerular lesions
a) capillary BM thickening
b) mesangial sclerosis
c) nodular glomerulosclerosis --> ball-like deposits of matrix in periphery --> ischemia and scarring
2. Arteriolosclerosis
3. Pyelonephritis - 22Describe the features of diabetic retinopathy1. Proliferative - hypoxia-induced VEGF production --> neovascularization and fibrosis; bleeding due to rupture of new capillaries
2. Non-proliferative - microangiopathy leads to weakening of capillary structure and hemorrhages, microaneurysms, dilations and edema (increased permeability)
- can lead to blindness - 23describe the features of diabetic neuropathy- peripheral and symmetric
- motor, sensory or autonomic (bowel, bladder) - 24What are the mainstays of therapy for type 1 and 2 DM?Type 1: insulin replacement therapy
Type 2: nonpharmacologic approaches such as dietary restrictions and exercise - 25How is glycemic control assessed over a long period of time?Measurement of HbA1C levels
Remains in blood for 2-3 months
Should be below 7% to reduce the risk for long-term complications - 26What cells form PanNETs?islet cell tumours
- 27What are the types of PanNETs? What is the most common type of PanNET?Insulinoma and gastrinoma
Insulinoma is most commooon - 28What are the clinical manifestations of insulinomas?secretion of large amounts of insulin --> hypoglycemia --> confusion, stupor, loss of consciousness
- 29Which tissues make up the gastrinoma triangle?Duodenum
Peripancreatic soft tissues
Pancreas - 30What are the clinical manifestations of gastrinomas?secretion of large amounts of gastrin --> gastric acid secretion --> gastric ulcers
- 31Describe the layers of the adrenal cortex and which hormones are produced whereouter --> inner
Glomerulosa = mineralocorticoids (aldosterone)
Fasciculata = glucocorticoids (cortisol)
Reticularis = sex steroids (estrogens & androgens) - 32what types of cells exist in the adrenal medulla? Which hormones are produced there?chromaffin cells
catecholamines - 33What are the 3 distinct hyperadrenal clinical syndromes?Cushing syndrome (hypercortosolism)
Hyperaldosteronism
Adrenogenital or virilizing syndromes - 34What are most common causes of hypercortisolism? What is the MOST common overall? What is the most common endogenous cause?1. Iatrogenic*** - administration of exogenous glucocorticoids
2. Hypothalamic-pituitary disease leading to excess ACTH secretion (CUSHING DISEASE) --> most common endog.
3. Secretion of ectopic ACTH by nonpituitary neoplasms
4. Adrenocortical neoplasms (adenoma or carcinoma) or hyperplasia - 35Describe the morphology of the pituitary gland and adrenal gland in Cushing disease?Pituitary:
1. microadenoma not causing mass effect
OR
2. corticotroph hyperplasia secondary to hypothalamic CRH secreting tumor
Adrenal:
bilateral nodular cortical hyperplasia
secondary to ACTH secretion - 36Which tumors are responsible for the secretion of ectopic ACTH? What is the morphology of the adrenal gland?Mainly small cell carcinoma of lung
Also carcinoids, medullary carcinoma of thyroid, PanNETs
Bilateral cortical hyperplasia - 37Hypercortisolism due to primary adrenal neoplasms and primary cortical hyperplasia are designated _______ACTH-independent Cushing syndrome
- 38What are the laboratory findings of adrenal Cushing syndrome?elevated cortisol and low ACTH
cortisol induces a negative feedback on ACTH production - 39What are the laboratory findings of pituitary Cushing syndrome?high ACTH and high cortisol
- 40Describe the morphology of the adrenal glands when hypercortisolism is a result of exogenous glucocorticoid administration (iatrogenic)bilateral cortical atrophy due to lack of stimulation of reticularis by ACTH
- 41Describe the morphology of the adrenal glands with functioning (cortisol producing) tumors?High cortisol production suppresses endogenous ACTH which leads to atrophy of the adjacent adrenal cortex and that of the contralateral gland
- 42What are the clinical manifestations of cushing syndrome?- hypertension
- weight gain
- accumulation of fat in posterior neck and back (Buffalo hump)
- decreased muscle mass due to atrophy of myofibers
- secondary diabetes
- loss of collagen due to catabolic effect on proteins --> fragile, easy bruisable ski
- bone resorption --> osteoporosis
- suppressed immune system
- extraadrenal Cushing (high ACTH) --> hyperpigmentation of skin - 43Define primary hyperaldosteronismautonomous overproduction of aldosterone by the adrenal glands
inhibits the RAA system - 44What are the causes of primary hyperaldosteronism in order of prevalence?1. Bilateral nodular hyperplasia
2. Adrenocortical neoplasm
a) aldosterone-producing adenoma (Conn syndrome)
b) carcinoma
3. Overactivity of aldosterone synthase gene - 45Define secondary hyperaldosteronismAldosterone production occurs secondary to activation of RAA system
- 46Describe the causes of secondary hyperaldosteronism- decreased renal perfusion (ex. renal artery stenosis)
- hypovolemia and edema (nephrotic syndrome, congestive heart failure, cirrhosis)
- pregnancy (caused by estrogen-induced increase in renin) - 47What are the characteristic features of aldosterone-producing adenomas?cytoplasmic inclusions called spironolactone bodies
- 48What are the effects of aldosterone on the kidneys?Na+ retention and K+ excretion
- 49What are the clinical manifestations of hyperaldosteronism?hypertension!!
- can lead to cardiovascular compromise, increased risk of stroke/MI
hypokalemia - 50Describe the therapy for hyperaldosteronism caused by: adenomas hyperplasia secondary causessurgical excision
aldosterone antagonist --> spironolactone
treatment of the underlying cause of RAA hyperstimulation - 51What androgens are produced by the adrenal glands? What regulates their production?dehydroepiandrosterone and androstenedione --> converted to testosterone in peripheral tissue
regulated by ACTH - 52What are the most common adrenal causes of androgen excess?1. adrenocortical neoplasms - more likely to be carcinomas than adenomas
2. congenital adrenal hyperplasia - rare - 53Define and describe the pathogenesis of congenital adrenal hyperplasiaHereditary defect in an enzyme involved in adrenal steroid biosynthesis particularly cortisol
low cortisol production --> increase in ACTH --> adrenal hyperplasia --> increased production of cortisol precursors --> channeled into androgen synthesis due to lack of enzymes for cortisol - 54What is the most common enzymatic defect in congenital adrenal hyperplasia?21-hydroxylase
- necessary for the production of cortisol and aldosterone but NOT sex steroids
- thus, precursors are shuttled towards sex hormone production - 55What are the clinical manifestations of congenital adrenal hyperplasia?depends on the severity of the enzymatic defect
Males: enlarged external genitalia, precocious puberty
Females: masculinization, clitoral hypertrophy, oligomenorrhea, hirsutism, acne
when enzymatic deficiency is severe --> can also result in concomitant aldosterone and cortisol deficiency (hypotension) - 56What is the treatment for congenital adrenal hyperplasia?exogenous glucocorticoids
- will replace missing cortisol
- also will suppress ACTH reducing sex steroid production
mineralocorticoids for aldosterone-insufficient variants - 57What are the causes of primary ACUTE adrenocortical insufficiency?1. sudden withdrawal of corticosteroid therapy
- steroids cause atrophy of the adrenal gland and when withdrawn, the adrenals cannot compensate
2. stress in patients with chronic underlying insufficiency
3. massive hemorrhage into the gland
- DIC, anticoagulant therapy, pregnancy, Waterhouse-Friderichson syndrome (result of N.mengitidis infection leading to septicemia inducing DIC or endotoxin mediated vasculitis and bleeding) - 58Define chronic primary adrenal insufficiencyAddison disease
Progressive destruction of the adrenal cortex - 59What are the causes of Addison disease?1. Autoimmune adrenalitis
2. Infections
- TB
- AIDS
3. Metastatic cancer- derived mainly from lung and breast - 60Describe autoimmune adrenalitisoccurs as a result of mutations in AIRE gene
lack of expression of adrenal cortical antigens in the thymus --> allows survival of - 61Define secondary adrenocortical insufficiencyAny disorder of the hypothalamus or pituitary which reduced the output of ACTH
- 62How can primary and secondary adrenocortical insufficiency be distinguished?Administration of exogenous ACTH in:
1. Primary --> no increase in cortisol production
2. Secondary --> cortisol increases - 63Describe the morphology of the adrenals in adrenocortical insufficiency Primary and secondaryPrimary autoimmune - shrunken
TB - granulomatous
Metastatic carcinoma - enlarged, normal architecture obscured by infiltrating neoplasm
Secondary - shrunken, atrophy of cortical cells - 64Describe the clinical manifestations of adrenocortical insufficiencynormally do not appear until 90% of the adrenal cortex is compromised
- progressive weakness
- fatigability
- hypoglycemia
- Primary disease (with high ACTH) - hyperpigmentation of skin and mucosa
- decreased aldosterone with hyperkalemia, hyponatremia, hypovolemia and hypotension
- decreased sex steroids
- Secondary - normal aldosterone but low androgen and cortisol output - 65Adrenal adenomas are associated with_______ Adrenal carcinomas are associated with ________a) Cushing syndrome and hyperaldosteronism
b) Virilizing syndromes - 66What cells make up pheochromocytomas? What is the normal function of these cells?chromaffin cells
production of catecholamines - 67Describe the "rule of 10" for pheochromocytoma10% are bilateral
10% are extraadrenal (called paragangliomas)
10% are malignant
10% do NOT cause hypertension - 68What gene mutations are associated with familial pheochromocytoma?RET (MEN2)
NF1
VHL
succinate dehydrogenase complex --> stabilizes HIF-1a promoting tumorigenesis - 69What are the clinical manifestations of pheochromocytomas?hypertension! (in 90% of patients)
- can be paroxysmal episodes of chronic elevated BP
- paroxysms can lead to catecholamine cardiomyopathy or catecholamine-induced myocardial instability and ventricular arrhythmias - 70How are pheochromocytomas diagnosed?based on increased urinary excretion of free catecholamines and metabolites like vanillylmandelic acid and metanephrines
- 71what is the most common solid EXTRACRANIAL tumor of childhood?neuroblastoma
- adrenal medulla
- retroperitoneal sympathetic ganglia - 72Define MEN syndromegroup of inherited diseases caused by proliferative lesion of multiple endocrine organs
- 73What are the distinctive features of tumors arising in MEN syndrome that are not shared by the sporadic counterparts:- occur at a younger age
- arise in multiple organs
- multifocal (even in the same organ)
- preceded by an asymptomatic stage of endocrine hyperplasia
- more aggressive - 74What is the mutation associated with MEN-1?loss-of-function mutation in MEN1 tumor suppressor gene which encodes "Menin"
loss of menin function leads to endocrine neoplasia - 75Which organs are involved in MEN13 P's:
1. Parathyroid
- usually initial manifestations
- hyperplasia and adenomas
2. Pancreas
- most common cause of death
- functional tumors that secrete tumors
3. Pituitary
- prolactin-secreting macroadenoma - 76Describe the genetic basis of MEN2gain-of-function mutation of RET
MEN2A and 2B differ based on single amino acid change - 77What organs are involved in MEN2AThyroid - medullary carcinoma
Adrenal medulla - pheochromocytoma
Parathyroid - hyperplasia with manifestations of primary hyperPTH - 78What organs are involved in MEN2B? How does it differ from MEN2AThyroid - medullary carcinoma which is multifocal and more aggressive
Adrenal medulla - pheochromocytoma
NO HYPERPTH
Extraendocrine manifestations - ganglioneuromas, marfanoid habitus (overly long bones of axial skeleton)
Informações
- Descrição
- Pathology FlashCards sobre Pathology 2 - Endocrine, criado por Emilia Mijatovic em 29-07-2020.
- Criado por
- Emilia Mijatovic
- Visualizações
- 0
- Avaliação