Pathology - Endocrine

Front 1

Normal range for blood glucose

Back 1

70-120 mg/dL

Front 2

Requirements for diagnosis of diabetes mellitus

Back 2

*random glucose over 200 with classical signs and symptoms
*fasting glucose over 126
*Abnormal OGTT (over 200 - 2 hrs after standard carb load)

Front 3

Difference between T2DM and T1DM

onset
weight

Back 3

T1DM - <20 yrs, normal weight

T2DM - >30 yrs, obese

Front 4

Difference between T2DM and T1DM

insulin level
Abs to islets cells
ketoacidosis

Back 4

T1DM: markedly decreased insulin; anti-islet cell antibodies; +ketoacidosis

T2DM: (early) increased insulin, (late) moderate to decreased insulin; no islet Abs; rarely ketoacidotic

Front 5

Difference between T2DM and T1DM

pathogenesis

Back 5

T1DM: autoimmune destruction of β-cells mediated by T cells and humoral mediators (TNF, IL1, NO)

T2DM: Insulin resistance in skeletal muscle, adipose, liver; β-cell dysfunction and relative insulin deficiency

Front 6

Difference between T2DM and T1DM

islet cells

Back 6

T1DM: insulitis early; marked atrophy and fibrosis; β-cell depletion

T2DM: NO insulitis; Focal atrophy and amyloid deposition; Mild β-cell depletion

Front 7

Most important stimulus for insulin synthesis and release

Back 7

Glucose

Front 8

Is glucose uptake into pancreatic β cells insulin dependant?

Back 8

NO

Front 9

What transporter is used in glucose uptake into pancreatic β cells

Back 9

GLUT-2

Front 10

Steps in glucose mediated insulin release from β cells

Back 10

1. Glucose uptake by GLUT-2
2. Glucose metabolism and ATP generation inhibits ATP sensitive K channel on β cell membrane
3. Deploarization of β cell
4. Ca uptake
5. immediate phase of insullin release
6. protracted delayed phase of insulin synthesis and release (if stimulus continues)

Front 11

What other agents can stimulate insulin release?

What can they not do though?

Back 11

intestinal hormones (which ones?)
leucine
arginine

synthesis of insulin

Front 12

These react against β cell antigens and cause cell damage in T1DM

Back 12

T lymphocytes

Front 13

Difference in mechanism of CD4 and CD* destruction of β cells

Back 13

CD4: (TH1 subset) activate macrophages --> delayed hypersensitivity

CD8: direct killing; also activate macrophages

Front 14

these are cytokines that damage β cells in T1DM

Back 14

IFN-g from Tcells
TNF and IL1 from macrophages

Front 15

Auto antibodies to β cell antigens particularly ______ are detected in 70-80% of patients

Back 15

GAD glutamic acid decarboxylase

Front 16

The most important genetic association in T1DM is

Back 16

class II MCH HLA locus

also important are the insulin gene and the gene encoding the T-cell inhibitory receptor (CTLA-4)

Front 17

viral agents implicated at potential triggers for autoimmune attack in T1DM

how do they work?

Back 17

coxsackievirus
mumps
measles
cytomegalovirus
rubella
infectious mononucleosis

produce protiens that mimic self antigens. immune response to viral protein cross reacts with self tissue

Front 18

two main metabolic defects that characterize T2DM

Back 18

insulin resistance
β cell dysfunction

Front 19

this is the strongest environmental factor associated with T2DM

Back 19

obesity

Front 20

Possible factors influencing insulin resistance in obesity:

Back 20

*high levels of FFA in blood (interferes w insulin function)
*cytokines from adipose (leptin, adiponectin, resistin)

Front 21

function of thiazolidinediones in diabetic treatment

Back 21

activates adipocyte nuclear receptor (PPAR-g) --> modulates gene expression --> reduces insulin resistance

Front 22

qualitative β cell dysfunction in T2DM includes

Back 22

*loss of normal pulsatile, oscilating pattern of insulin secretion
* attenuation of first rapid phase of insulin secretion triggered by glucose

Front 23

quantitative β cell dysfunction in T2DM
includes

Back 23

decreased β cell mass
islet degeneration
deposition of islet amyloid

Front 24

5 cell types and secretions of anterior pituitary

Back 24

somatotrophs - GH
lactotrophs - Prl
corticotrophs - ACTH
thyrotrophs - TSH
gonadotrophs - FSH, LH

Front 25

this inhibits release of prolactin

Back 25

dopamine

Front 26

cell type and secretions of posterior pituitary

Back 26

pituicytes (modified glial cells)

ADH (vasopressin)
oxytocin

Front 27

in most cases HYPERpituitarism is intrinsic to the pituitary and caused by:

Back 27

functional adenoma within anterior lobe

Front 28

excess production of anterior pituitary hormones is most often caused by:

other causes:

Back 28

adenoma in anterior lobe


primary hypothalamic disorders
carinoma (rare)

Front 29

Why do functional pituitary adenomas usually produce only one type of hormone?

Back 29

usually composed of single cell type.

some generate more than one hormone - eg. GH, Prl

Front 30

How would a pituitary adenoma cause hypopituitarism

Back 30

destroying adjacent normal parenchyma

Front 31

micro and macro adenomas are less than/greater than:

Back 31

10mm

Front 32

microsopicaly these lesions appear as uniform monomorphous cell populations. neoplastic cells are arranged in sheets, cords, nests and have scanty reticulin network.
membrane bound secretory granules present in cytoplasm of most cells

Back 32

adenoma of anterior pituitary

Front 33

most common functional pituitary tumor (30% of all adenomas)

Back 33

prolactinoma

Front 34

characteristics of prolactin secretion by prolactinoma

Back 34

efficient - even microadenomas secrete enough Prl to cause hyperprolactinemia

serum concentrations tend to correlate with size of prolactinoma

Front 35

histologic appearance of prolactinoma

Back 35

microadenoma composed of sparsely granulated acidophilic or chromophobic cells

Front 36

other causes of hyperprolactinemia besides prolactinoma

Back 36

*pregnancy (peak at delivery)
*lactotroph hyperplasia

Front 37

what causes pathologic lactotroph hyperplasia?

Back 37

interference of normal dopamine inhibition of Prl secretion due to damage of dopaminergic neurons of hypothalamus, pituitary stalk section (head trauma), or drugs that block dopamine receptors on lactotroph cells

Front 38

Why would mild serum elevation of Prl in a patient with a pituitary adenoma not necessarily suggest a Prl-secreting tumor?

Back 38

any mass in suprasellar compartment may disturb normal inhibitory influence of hypothalamus (dopamine) on Prl secretion - "stalk effect"

Front 39

clinical features of pt with prolactinoma

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amenorrhea
galactorrhea
loss of libido
infertility

Front 40

why is pituitary adenoma more easily detectable in women than men?

Back 40

menses are more readily disrupted by hyperprolactinemia (prolactinoma or stalk effect)

Front 41

acromegaly or gigantism is associated with this type of pituitary tumor

Back 41

GH (somatotroph cell) adenoma

Front 42

microscopically this type of tumor is composed of densely granulated cells which appear acidophilc or chromophobic; sparsely granulated variants contain a "fibrous body"

Back 42

GH (somatotroph) adenoma