ENDOCRINE Flashcards
Four major cells found in pancreas
Beta - insulin
alpha - gluccagan
delta - somatostatin
PP - pancreatic polypeptide that stimulates secretion of gastric and intestinal enzymes, inhibit intestinal motility
two minor cells
D1 cells - VIP
Enterochromaffin cells - serotonin
zollinger ellison syndrome
gastrinomas usually in small intestine and pancreas
present with chronic diarrhea and duodenal ulcer
increase thickness of oynthnic mucosal fold due to in rease in parietal cells
hyperplasia of mucous neck cells
dysplastic nodules or rare carcinoid tumours
what conditions are somatostatinomas associated with
DM
cholelithiasis
steatorrhea
hypochlorhydria
carcinoid tumor
from enterochrommafin cells
which muscle is the major insulin responsive site for PP glucose utilization
skeletal muscle
hyperglycemic in diabetes result from
defect in insulin secretion
defects in insulin action
both commonly
normal range for blood glucose
70 - 120mg dl
rbs value for diabetes
A random glucose > 200 mg/dL, with classical signs and symptoms
fbs value
A fasting glucose > 126 mg/dL on more than one occasion
ogtt value
An abnormal oral glucose tolerance test (OGTT), in which the glucose is > 200 mg/dL 2 hours after a standard carbohydrate load
primary diabetes
Type I – IDDM / Juvenile – 10%.
Type II – NIDDM /Adult onset – 80%.
MODY – 5% maturity onset of diabetic of the young - Genetic
secondary DM
Islet destruction
IPED
type 2 diabetes
combination of peripheral resistance to insulin and inadequate secretory response by the pancreatic b cells(relative insulin deficiency)
where is preproinsulin synthesized
RER
Which transport protein mediate uptake of glucose by pancreatic b cells
GLUT2
Insulin independent
mitogenic pathway of insulin responsible for
mitogenic effects of insulin and insulin like growth factors
Cell growth, proliferation, gene expression
metabolic effects on insulin mediated by
PI3K
synthesis of lipids, proteins, glycogen, cell survival and proliferatio
GLUT 4
insulin dependent
type 1 dm mediated by which lymphocytes
t lymphocytes
gene implicated in type 1 dm
hla - dr3 dr4
6p21
insulin resistance
to effects of insulin on glucose uptake, metabolism, and storage
abnormalities in insulin signalling pathway
Down-regulation of the insulin receptor
Decreased insulin receptor phosphorylation and tyrosine kinase activity
Reduced levels of active intermediates in the insulin signaling pathway
Impairment of translocation, docking, and fusion of GLUT-4-containing vesicles with the plasma membrane
adipokines like leptin adiponectin resistin retinol binding protein 1
Leptin - acts on CNS receptors to induce satiety
Adiponectin – Cause hypoglycemia,
Resistin – induce hyperglycaemia
Retinol binding protein 4 – induce hyperglycaemia
how is ppary activated and how does it work
activated by thiazolidinediones
PPARγ binds to DNA and activate transcriptin of genes that increase storage of free fatty acids in adipocytes
monogenic forms of diabetes
MODY
primary defect in B cell function that occurs without B cell loss
affecting either b cell mass and or insulin production
genetic
mitochondrial diabetes
diabetes associated with insulin gene or insulin receptor mutations
short term complicatioons
metabolic
Hypoglycemia
Diabetic Ketoacidosis
Non Ketotic hyperosmolar diabetic coma
Lactic acidosis
long term complications
angiopathy
Angiopathy, Retinopathy, Nephropathy, Neurophathy
Macrovascular disease
mi, stroke, lowee extremity gangrene
microvascular disease
retinopathy, nephropathy, neuropathy
what are the infections due to
microangiopathy and ischemia
immmunosuppression
hyperglycemia
distinct metabolic pathways involved in long term diabetic complications
Formation of Advanced Glycation End Products
Activation of Protein Kinase C
Intracellular Hyperglycemia with Disturbances in Polyol Pathways
key things in ages
non enzymatic
intracellular glucose derived dicarbonyl precursors
amino intracellular and extracellular proteins
cross linking between polypeptides
collagen type one in large vessels
type 4 in basement membrane
result of crosslinking
decreased elasticity of vessel - shear stress and endothelial injury
decreased endothelial cell adhesion and increases fluid filtration
AGE proteins
resistant to proteolytic digestion
age modified matrix
trap non glycated plasma or interstitial proteins
age receptors on which cell
endo cell
mesangial cell
macrophages
what does binding to plasma proteins to RAGE do
activation and nuclear translocation of nfkb
biologic effect off AGE receptor signalling
Release of cytokines and growth factors from macrophages and mesangial cells (insulin-like growth factor-1, TGF-β, platelet-derived growth factor, VEGF);
Increased endothelial permeability;
Increased procoagulant activity on endothelial cells and macrophages
Enhanced proliferation and synthesis of extracellular matrix by fibroblasts and smooth muscle cells.
which tissues do not require insulin for glucose transport
nerve
lense
kidney
blood vessels
Potential mechanisms of microvascular damage and malfunction in the polyol pathway include
Sorbitol-induced osmotic stress due to accumulated sorbitol,
Altered or decreased Na/K-ATPase activity,
myo-inositol depletion with impaired phosphatidylinositol metabolism,
Increased prostaglandin production, and
Alterations in protein kinase C isoform activity
cotton wool spots
diabetic retinopathy
proliferative retinitis
neovascularisation haemorrhagic fibroplasia retinal detachment laser cauterization
protein kinase c
Production of VEGF
vasoconstriction
vasoconstrictor endothelin – 1
vasodilator Enos
Fibrogenesis – TGF B
Procoagulant
Pro inflammatory cytokineHormones that trigger biochemical signals upon interacting with cell-surface receptors are classified into two
peptide hormones - growth and insulin
small hormones - adrenaline
binding of these hormones to cell surface receptors leads to
an increase in intracellular signaling molecules, termed second messengers, such (cAMP);
production of mediators from membrane phospholipids, such as inositol 1,4,5-trisphosphate or IP3;
shifts in the intracellular levels of ionized calcium.
example of hormones that diffuse across plasma membrane to bind to ic receptors
progesterone estrogen glucocortic steroids thyroxine
weight of pineal gland
100 - 180mg
cell in pineal and function
epithelial like pphotosensory neuroendocrine melatonin jet lag
name of tumor in pineal gland
of embryogenic origin
rare pinealomas
pineacytomas
pineablastomas
where adenohypopyhsis is derived from
rathke pouch
adeno about 80 % of gland
which of the releasing factors are inhibitory
PIF
dopamine
somatostatin
3 Major cells types based on appearance in h e stainin
acidophils - bright pink
GP
Basophils - purple
thyroid stim, acth, gondo
chormophobes - pail stainining
not assted with specific hormone secrn
5 cell types based on antibodies
somatotrophs - GH half of all hormone producing
lactotroph/ mammotrophs - prolactin
cortico - ACTH MSH
thyrotrophs - TSH
gonadotrophs - FSH, LH
Cells in neurohypophysis
pituicytes..modified glial cells
adh produced in response to
Increased plasma osmotic pressure,
Reduced left atrial distention,
Exercise and certain emotional states
pituitary disoders manifest as
hypo
hyper
local mass effect
hyperpituitarism
Pituitary adenoma – most common cause
not always functional
Pituitary hyperplasia
Carcinoma of the anterior pituitary
Paraneoplastic syndromes
pituitary adenoma occur in which type of MEN
MEN 1
mutations in pituitary adenoma
GNAS 1 for g protein
ras ongnene
cmyc oncogene
gs alpha bound to what in inactive state
gdp
cAMP acts as which type of stimulus and regulated by
mitogenic
GTPase
alpha subunint of gs encoded by
which chromosome
GNAS gene
20q13
there is no GNAS mutation in which trophs
lacto
thyro
gondo
gnas mutation is more where
somato
cortico minor
micro of pituitary adenoma
uniform cells in diffuse sheet with absence of supporting reticulin sheet
hypopituitarism
Pituitary masses Pituitary surgery or radiation Pituitary apoplexy Ischaemic necrosis or Sheehan’s syndrome (post partum necrosis) Genetic abnormalities
adrenals mass
4g each
adenoma and carcinoma of adrenals..which is heavier
Carcinoma
types of adrenal hyperplasia
diffuse less heavier
nodular
what avors malignancy in adenocortical neoplasms
anaplasia
mitotic activity
adenoma
carcinoma
seen in
hyperaldosteronism
cushing
virilizing neoplasm
can the functional status of adrenal cortical adenom be predicted from gross or micro app
no
xtic of neoplastic cells in adrenal cortical adenoma
vacuolated due to presence of intracytoplasmic lipid
necrosis seen in adenoma or carcinoma
carcinoma
forms of cushing syndrome
pituitary
adrenal
paraneoplastic
iatrogenic
deficiency in congenital adrenal hyperplasia
21 - hydroxylase
recessive
leads to virilization
micro features in congenital adrenal hyperplasia
hyperplastic acessory nodules
lipid depleted cutp[;as,
hypoadrenalism causes
pimary
acute - waterhouse friderichsen..sudden withdrawal from steroids
chronic - Addison
secondary
acth def
kidney in waterhouse
dark
hemorrhagic
shrunken
cortical architecture not discernible
causes of addison disease
autoimmune - most common cause tuberculosis metastatic..lung and breast fungal amyloidosis hemachromatosis
cells secreting catecholamines in pheochromocytoma
chromaffins
are pheochromocytoma sporadic
yeah 90%
presentation in pheochromo
hypertension
tachycardia
sweating
anxiety
is hypertension correctable in pheo
yes
when is malignancy established in pheo
metasasis only
nest with alveoli pattern known as zelllballen
micro of pheo
xtic in MEN
Inherited proliferative multifocal asymptomatic stage of hyperplasia younger age agrresive recur
MEN 1
Pituitary
parathyroid
pancreatic islets
mutant gene locus in MEN
11q13 menin
MEN 2A
Parathyroid
Adrenal..pheo
Thyroid
mutant gene locus in MEN 2A
RET protooncogene
variant of MEN 2A
familial medullary thyroid cancer
MEN 2B
adrenal pheo
thyroid
extraendo..mucocutaneous ganglinoneuromas and marfanoid habitus
mutant gene locus
RET protooncogene
