Pancreas And Adrenals Flashcards
Endocrine pancreas
Actress vasculature andsend to target organs
Islet of langerhans
Discrete collection of small blue islands in neck and tail of pancrease
Very vascular bc endocrine
PP celll
Secrete pancreatic polypeptide
D1cell
Secrete VIP:vasoactive intestinal polypeptide
Rare
Glucose homeostasis
Regulating insulin and glucagon
Glucagon
Mobiliza glucose primarily from liver
Insulin receptor
RTK MEK to MAP kinase
rek PI3K AKT
Both increase glycogen lipid/protein synthesis
Decreases lipolysis
Cel growth and differentiation** anabolic.
C peptide
Proinsulin is cleaved toform insulin and c peptide
C peptide is a marker of endogenous insulin
-can differentiate from insulin administrations as a pharmaceutical agent
Incretins
Oral*** glucose stimulated release of GLP-1 and GIP
Which go straight to pancreas for early onset insulin release and inhibitit glucagon and glucose production
Early and potent recognize blood sugar will go up and early insulin secretion
MOA incretins
Stimulate insulin release and inhibit glucagon release resulting in lower blood glucose
Inactivation incretins
Dipeptidyl peptidase-4 DPP4
*drugs ending in glipton
Diabetes mellitus
Defective insulin secretion or effect
A1c
> 6.5
FPG
> 126
OGTTT
> 200
RPG
> 200
Asians
Low diabetes but if break out south asians (high)
East Asian 9low )
ASian Indians
High as African Americans
Type 2 diabetes in kids under 20
10-19
Type 1 diabetes age
1-19
Who gets type 2 diabetes
More likely in teenage population than type I
Onset type 1and 2
1-childhood and
2-increasing in childhood
Type 1 and 2 cause
1-autoimmune T. Cell selection and regulation leading to breakdown and self tolerance
2-insulin resistance in peripheral start (no autoantibodies ) but increasing in adolescents!!
Pathology
Insulitis and autoantibodies present (inflammatory infiltrate) B cell depletion and islet atrophy
2-no insulinitis; amyloid depositio in islets mild B cell depletion
Type 1 histology
Failure of T cell self tolerance-see t lymphocytes directed against antigens on the pancreativ beta cell
MHCII type I
6p21 for 50%
Development of type 1
Lack of insulin from immune destruction of islet cells. Must be over 90% destroyed to give overt symptoms
Only occurs when mass is 10% of normal
Type 2 diabetes
Insulin resistance and B cell dysfunction
Why are they resistant to insulin
Obesity
Metabolism of adipose tissue cause FFA which are toxic and go into cell and disrupt insulin pathway.
Adipokines-some protective some negate insulin effect(these are elaborated when excess adipose tissue is present)
Inflammation -damages cells targeted and pancrease itself
Insulin resistance over time
Secretion increases initially to compensate
Then decreased wear out and give T2DMD
Genetics T2DM
More likely to have first degree relative with T2DM
As lose insulin
Get islet B cell failure
What has to be present to T2DM to cause symptoms
Beta cell dysfunction!!!
Beta cells are exhausted
MODY
Onset childhood, nonketo, increased blood insulin but no islet antibodies
Monogenic——from mutation inhibiting glucokinase
Not autoimmune not insunilnitis
Gestational diabetes
Pregnancy promotes a hormonal state with diabetogenic properties
Risk gestational diabetes to mom
C section
Ribs to fetus
Neonatal hypoglycemia->seizures->brain damage
Macrosomia
Congenital malformation
Stillbirth
***screen for it!!
First prenatal visit
Measure FPG, HBA1c or random plasma glucose
>6.5
>126
>200
Treat and follow up as for preexisting diabetes
24-28 week screen that passed first
OGTT in morning after overnight fast
Fasting >92
1 hour after >180
2 hour >153
Have it and treated
T1 and T2
Hyperglycemia
Triad of T1
Polyphagia, polyuria, polydipsia
Severe-ketoacidosis
T2 clinical
Fatigue, vision changes
4 T in kids t1D
Toilet-glucose pulls fluid from tissue osmotic
Thirsty-glucose pulls fluid from tissue
Tired -lack of sugar in cells!!
Thinner-without energy sugars supply lose weight
Hunger-without glucose need more food
Fruity breath-keno from burning fat instead of glucose
Young kid brought in is it type 1 or 2? How tell? What test?
Autoantibodies in caucasion More reliable in caucasion for type 1 . But if have autoantibodies out there then type 1. Harder to tell if not caucasion
HLA DR/DQ on chomosome 6
Diabetic ketoacidosis
Type 1, severe acute diabetic complication
Can be presenting feature of T1DM in adult and kid
Why get DKA if have diabetes
Non compliance
Precursor infection-pneumonia, UTI
Triad of ketoacidosis
Hyperglycemia, ketonemia, metabolic acidosis
Why get ketoacidosis
Effect of hyperepinephric state (not using glucose so get glucagon for gluconeogenesis and insulin defiency proton FFA release)
Kidney dumping ketones and osmotic diuresis so dehydrated
SHOCK, DEHYDRATION: secrete more epinephrine so spiral over and over
EPINEPHRINE
Accumulate ketones
Acetoacetic acid and beta hydroxybutarate in urine
DKA
Hyperglycemia, ketonemia and acidosis
Resulting in
Dehydration, polydipsia, polyuria/ketouria
Presenting signs
Nausea/ vomiting, tachycardia, kussmal respiration
What do to help metabolic acidosis
Respiratory kussmall respiration breathing a lot blowing CO2 off
Treat DKA
Insulin, hydration, potassium!!
All hypokalemia even if K high!!
Usually in RBC but when insulin drop K leave cells and treat with insulin K back into cells so always hypokalemia so moment give insulin need to be ready to treat with K
Hyperglycemia hyperosmotic syndrome
Acute hyperglycemia crisis in T2DM.
Culmination of prolonged insulin defiency
- increased gluconeogenesis
- decreased glucose uptake in peripheral tissues
B cells not making insulin very hyperglycemia
Who more hyperglycemia DKA or HHS
HHS
8T1 shunt to ketogenic these patients elaborate
Presenting HSS
Glucose>500
Severe dehydration
Hyperosmolarity >350-> obtundation, coma
Impaired renal function
Older person in facilitated care facility and cant take care and worse control of diabetes become stuporous and spiral out of control and can be comatose when come to attention
Ketones in HSS
NOOOOOO
DKS vs HHS pH
<73
>7,3
Osmolality DKA HHS
<320, >320
Hyperglycemia DKA HHS
> 250 >600
Ketones DKA HHS
Present, rare
DKA
Anion gap acidosis
Ketonemia
Ketouria
Hyperglycemia
HHS
Hyperglycemia
High osmolality
Dehydration
Altered mental status
HA1C
Glucose fasten to RBC =irreversibly glycosylation of the hemoglobin A1C—-determines for past month
Major complications of diabetes
Microvascular and macrovascular , lower extremity gangrene, neuropathy (microvasular complication-why extremity disease is so bad don’t know when cut foot or when there’s an infection)
*most common cause of death in diabetics: MI
Most common cause of death in diabetics
MI
Chronic hyperglycemia causes
Stroke, MI, lower extremity gangrene
Neuropathy
Might be having heart attack but manifest heart burn or something
Advanced glaciated end products
Effect gene expression and protein function
-cytokines (TGFB and VEGF)and growth factors elaborated, ROS , procoagulant activity, cross linking of matrix proteins -proarthegenic
End stage renal disease
Usually from diabetes, screen with albumin and urine
-direct damage to glomeruli, renal vascular lesions, arteriosclerosis, pyelonephritis
Glomeruli diabetes
Kimmelsteil wilson nodule -matriculates in glomeruli(PAS stain pink nodules)
Thick basement membrane-
Diabetic nephropathy
Urine albumin tests
Macroalbumin->300
Microalbumin-small amount 30-300
Nephropathy!losing function
Diabetic retinopathy
Hemorrhages , aneurysms, cotton spots, abnormal growth of blood vessels, hypoxia, blindness
Other-cataracts, glaucoma
Other eye complications
Cataracts, glaucoma
Neuropathy
Peripheral, autonomic, diabetic mononeuropathy
Decreased immune response diabetes
Cellulitis, pneumonia, pyelonephritis
Pancreatic neuroendocrine tumor
Gross appearance yellow tan
Predilection for pancreatic neuroendocrine tumors
EM-secretory granules
Insulinoma
Amyloid ***
Small and secretes lot of insulin
C peptide levels can make the diagnosis
Hypoglycemia and insulin levels high!!
Then check c peptide levels
C peptide increased
Gastrin OA
Zollinger ellison
Triad-islet cel tumor, gastric acid hypersecretion, peptic ulceration not responding to therapy for peptid ulcer think of gastrinoma HYPERSECRETION OF GASTRIC ACID AND HYPERSECRETION
Ulcers do not respond to conventional therapy
-clue to clinical diagnosis
Somatostainoma
Diabetes, cholelithiasis, steatorrhea->hard to diagnose
Somatostatin functions as a paracrine regulator, so manifestations are typically inhibitory
- reduced insulin
- reduced gallbladder motility
- reduced exocrine pancreatic secretions
When somatotstatinoma come to attention
Bit later, but at time a lot are metastatic !
Glucagonoma
Mild diabetes
Rash-necrolytic migratory erythema
-groin, lower extremities
4D
-diabetes, dermatitis, depression, DVT
Necrolytic migratory erythema
Pathogenomic rash consisting of erythema with superficial areas of spideamla necrosis, progressing to epidermal shedding, bullae formation, and crushsted erosions
VIPoma
Vasoactive intestinal pepdide:D1 cells
WDHA syndrome
Watery diarrhea, hypokalemia, achlorhydria
20% of patients will have flushing as well -what else gives you flushing and diarrhea
Flushing diarrhea
VIPoma or carcinoid
Look at K
Adrenal gland
Cortical and medullary zone
Cushing primary
High cortisol and low ACTH CRH
Obesity, striae, rounded face
ACTH dependent or independent
Adrenal gland and external stimuli
Very sensitive t being changed
Doing job of adrenals for them as shrink appear atrophic
ACTH dependent like cushing disease (adenoma) bilaterally hyperplastic
Primary adenoma of adrenals cortical
Hyperfunction benign come to attention bc hyperfunction
Adrenal cortical carcinoma
Larger! Weight >200
More likely symptomatic bc of how big they get ..very important clue
Hypercortisolism work up
Check ACTH
Low-adrenals for primary conditions
High pituitary or something
Primary hyperadrenalism
Elevated cortisol and corticotropin levels suppressed
Primary hyperaldosteronism (conns syndrome)
Hypertension 0refractoru HTN -adrenal mass and HTN -htn in young -severe HTN (>160/100 mmHg)
Hypokalemia
Hypomagnesia
Causes of conn
Most common is
Second adenoma
Familial-glomeruloasa cells respond
Conn increased what
ALDOSTERONISM
Secondary hyperaldosteronism
Increased RAAS
-diuretic use, decreased renal perfusion, arterial hypovolemia, pregnancy, renin secreting tumors
Aldosterone secreting adenoma
Small
Young 30-40
Spironolactone bodies
High incidence of ischemic heart disase
See adrenocortical cells and spironolactone bodies-pink concretions see not sure bc tend to see if patient is treated with spironolactone with surgery
Why use spironolactone aldosterone secreting adenoma
Spironolactone so get spironolactone bodies ,
HTN to ischemic heart disease in 30-40
Aldosterone secreting adenoma-primary hyperaldosteronism
How tell primary vs secondary hyperaldosterone
Plasma renin high in secondary low in primary (adrenal CT and adrenal vein sampling!)
Adrenogenital syndromes
Virilization
And congenital adrenal hyperplasia
Pituitary adrenogenital syndromes
ACTH stimulate androgens-cushing
Adrenal adrenogenital syndromes
Primary adrenal neoplasm
-adenoma, carcinoma (more common)
Carcinoma is virilizing
CAH
Inherited error of metabolism
-AR
Defective enzyme responsible for steroidogenic is
Impaired feedback to hypothalamus/pituitary, with resultant hyperplasia
90-95% caused by defiency of 21-hydroxylase
Decrease glucocorticoids CAH
ACTH up and go and make adrenal big! But last thing to occur really…
Most common CAH
21 hydroxylase defiency
Salt wasting of 21 hydroxylase
No mineralocorticoids or cortisol
Male and femal infants 21 hydroxylase
Salt wasting->hyponatremia
Hyperkalemia
Hypotension
In first weeks of life
Why females better for 21 hydroxylase
Can tell at birth when virilized
Long term 21 hydroxylase defiency
Adrenomedullary dysplasia: hypotension
What see with virilization
Fused labia and large clitoris and scrotal appearance of labia
Partial lack of 21 hydroxylase
Simple virilizing syndrome (without salt wasting
What have in simple virilization
Some mineralocorticoids and small amount of cortisol, not enough to prevent ACTH
Non classical late onset adrenal virilsm
Most common
Partial lack
- precocious puberty
- acne and hirsutism at time of puberty
Diagnose CAH
Serum 17 hydroxyprogesterone
ACTH stimulates test
Treat CAH
Glucocorticoids
- replenishes cortisol
- provides negative feedback for ACTH suppression
- no further overstimulation of androgen production
Mineralocorticoids as necessary
Adrenocortical insuffiency
Primary insuffiency
-loss of cortical cells, defect in homogenous
Secondary insuffiency
0hypothalamic-pituitary disease
-BPA suppression by extra adrenal steroid use
Chronic vs acute
Primary acute adrenocortical insuffiency
Adrenal crisis
Rapid withdrawal of steroids
Massive adrenal hemorrhage
Table 24-10
Relative adrenal insuffiency patient
ICU for meningitis and become hypotensive and not responding to fluid replacement …something given them inadequate HPA response to situation
Not a lot of CRH, corticotrophin and decreased cortisol
ICU aren’t alert or aware so observe what’s going on this can be fatal . Hypotension leads to shock death
Exogenous steroid withdrawal
Steroid administration results in suppression of acth production by the pituitary through negative feedback
If prolonged adrenal hypofunction atrophy
Rapid withdrawal of exogenous steroids results in adrenal insufficiency WHY GIVE STEROID TAPER DO NOT RAPID WITHDRAWAL
Adrenal hemorrhage
Sepsis-Waterhouse friedreich Sean syndrome
Neonatal period
Trauma
Postsurgical patients
Coagulopathy
How regocnize
Hypotension Abdominal pain Fever Nausea/vomiting Hyponatremia Hypoglycemia
Primary chronic adrenocortical insuffiency
Long duration of malaise, fatigue
Anorexia and weight loss
Joint pain
Hyperpigmentation of skin
Why hyperpigmentation adrenocortical insuffiency
Increase POMC from pituitary , which makes ACTH, MSH
MSH pigmentation
Nelson syndrome
Out adrenals pituitary secrete more acth and HYERPIGMENTATION
Addison
Primary adrenal insuffiency
-feeble heart, change in skin, languor and debility .org
Addison autoimmune?
Calcification adrenal glands
T most common cause of Addison when initially described
Primary chronic adrenocortical insuffiency
Most common-TB
Workwide-autoimmune
Most common in developed countries autoimmune
Autoimmune adrenalitis
> 70% of all cases of primary hypoadrenalism in the western world
APS1 APS2
APS1
Mutation in AIRE
-adrenalitis, parathyroiditis, hypogonadism, pernicious anemia
Mucocutaneous candidiasis (ab IL17 and IL22), ectodermal dystrophy
APECED autoimmune polyendocrine with candidiadisis and extodermal dystrophy
Autoimmune polyendocrine syndrome
Adrenalitis
Thyroiditis
Type 1 diabetes
Ectodermal dystrophy
Type 1
Terrible teeth and no nails..?
Presentation adrenocortical insuffiency lack of corticosteroids
Malaise, NV, hypoglycemia, refractory hypotension
Presentation of adrenocortical insuffiency lack of mineralocorticoids
Hyperkalemia, hyponatremia
Test adrenocortical insuffiency
Random cortisol and acth stimulation test
Adrenal metastasis
For carcinomas go into adrenals
Mucus pigmentation
Adrenal insuffiency
Tuberculous adrenalitis
Caseating granuloma multinucleated giant cell
Sheet of necrosis tuberculous adrenalitis
Autoimmune adrenalitis
Influx of lymphocytes bc autoimmune
Adrenal cortical neoplasia
Adenoma and carcinoma
Adenoma
Incidental on radiography
Functional
Carcinomas
Incidental on radiography
Functional
***Compression/invasion of adjacent structures virilizing
Can hemorrhage into self and present acutely PAINFUL if bleedinto self
Carcinoma vs adenoma
Size HUGE predictor to adrenal cortex
Adenoma small
Carcinoma huge 300grams
Adrenal medulla
Centrally located chromaffin cells
Responsible for catecholamines
Same as paraganglionic stuff
Sympathetic control
Histology adrenal medulla
Nests of endocrine cells when form tumors that’s what look like
Pheochromocytoma
HTN!
From catecholamines secretin from the tumor
10% rule
-10% are extra adrenal (paraganglioma), 10% bilateral, 10% in kids, 10% malignant, 10% not associated with HTN
25% rule
25% familial
How tell pheochromocytoma malignant
Metastasis
HTN with pheochromocytoma
> 90%
HA, palpitations, diaphoresis*** (sweating) all from catecholamines release
Acute-catecholamines
Chronic cardiomyopathy
Chronic pheochromocytoma
Cardiomyopathy
Test pheochromocytoma
Urine and plasma metanephrines
Myelolipoa
Benign fat and bone marrow, vary in size, can present with hemorrhage
May bleed into self and give pain
Adrenal incidentalomas
> 4 cm ..size matters (less than 4 adenoma)
Positive functional assays
- dexamethasone suppression test for hypercortisolism
- pheochromocytoma
- this checks for adenoma
CT enhancement characteristics
MEN1 gene
Men1 menin tumor suppressor gene
3 P of MEN1
Primary hyperparathyroidism
Pancreatic endocrine tumor-insulinoma and gastrinoma
Pituitary adenoma-lactotroph and somatotroph
May also get duodenal gastrinoma
Type 2A gene
Germline gain of function mutation in RET Porto oncogene
Tumors of MEN2a
Medullary thyroid carcinoma
Parathyroid hyperplasia
Pheochromocytoma
Type 2B gene
Germline gain of function utation in RET protooncogene
Tumors 2B
Medullary thyroid carcinoma
Pheochromocytoma
Mucosal neuromas
Familial medulary thyroid carcinoma General
-just one not multiple
Germline gain of function RET protooncogene oncogene
MEN physical 2B and
Marfan and can be cloud
Generalities of MEN
Patients develop tumors at younger ages
More likely to be b/l and multiple
Preceding hyperplasia is often seen
Tumors tend to be aggressive and recurrent
Pineal gland
Third eye-comprised of photoreceptor containing neural tissue
Melatonin secretion
Tumors of pineal gland
Germ cell tumors
Pineocytoma
Pineoblastoma
