pathology of the endocrine pancreas - hillard Flashcards
B cells secrete what?
what is its major effect
beta cells secrete insulin and the major effects are to lower blood glucose and increase glucose in tissues (fat and muscle)
a cells secrete what and what is its major effect
glucagon and its major effect is to increase blood glucose by glycogenolysis
delta cells secrete what cells and what is the major effect
somatostatin
and it causes decreased insulin and decreased glucagon
PP cells secrete
major effect
pancreatic polypeptide
decreased intestinal motility and increase intestinal enyzmes
D1 cells secrete what
major effect
increase blood glucose a lot and cause by glyconeogenosis
cause a watery diarrhea
enterochromaffin cells secrete what
major effects
serotonin
regulate mood/mental states
“carcinod syndrome- flushing, tachycardia, diarrhea)
diabetes is very common and affects the _ system the _, peripheral _ and kidney
it results in too much _ in the blood to due issues in insulin production or response
cardiovasculae
nerves
glucose
type 1 diabetes is more frequently seen in _ and is caused by _ descruction of pancreatic _ cells leading to hyperlgycemia, it often requires _ for treatment
children
autoimmune
beta
insulin
type 2 diabetes is seen in adults is caused by _ _ to insulin, it is most frequently seen in _ adults
peripheral resistance
obese
diabetes is present if
HbA1c=
fasting plasma glucose=
oral glucose tolerance test 2 hours=
randmon plasma glucose =
HbA1c=6.5
fasting plasma glucose= 126
oral glucose tolerance test 2 hours=200
randmon plasma glucose = 200**
all tests must be repeated a second time on a different day to confirm
2 times- expect random plasma glucose
hemoglobin A1c is used to determine _ blood glucose levels over the last _ months
HGBA1c
average
2-3
hemoglobin AB1c is the glycosylated form of hemoglobin becuase glucose binds to hemoglobin
type 1 diabetes is a type _ hypersentitivity reaction and is caused by a _ cell autoimmune reaction against _ cells
_ _ are created
type 4
T
Beta cells
islet autoantibodies
in type 1 diabetes T cells attack beta cell antigen: what antigens
insulin and glutamic acid decarboxylase
in order to diagnose type 1 diabetes you must test the presence of?
autoantibodies (islet)
what HLA types are associated with type 1 diabetes
HLADR3, 4, 8
breakdown in self tolerance to islet autoantigens
stages of type 1 diabetes
stepwise progression
presymptomatic normoglycemia
non-symptomatic elevated blood sugar levels
symptomatic diabetes
typw 2 diabetes pccurs due to _ resistance which prevents peripheral tissues from adequattely responding to insulin couples with _ cell dysfunctino
insulin
b cell
the most important risk factor for type 2 diabetes is?
obesity
how does obesity drive type 2 diabetes
it causes insulin resistance by increasing free fatty acids, inflammatory cytokines, and adipokines which inhibit peripheral response to insulin
what type of diabetes causes type 2 diabetes
central belly fat wrapped around abdomnial organs due to the portal vein being able to carrier free fatty acids to the liver causing insulin resistance in the liver and preventing glucose uptake
other than obesity what caused T2DM
sedentary lifestyle
genetics
high caloric intake
sleep disturbances
what adipokin is decreased in obesity
adiponectin
what is the purpose of adiponectin
it is beneficial in insulin utilization (it is decreased in obesity)
excess _ _ _ in obesity will inhbit the peripheral reponse to insulin but are also proinflammatory and secrete cytokines like _
FFA
IL-1
in T2DM the initial reposne to an increased peripheral resistance is beta cells _ insulin production but eventually there is beta cell _ and ultimately failure
increase
dysfunction
failure= T2DM
histologically _ deposition is seen in T2DM as a result of _ secretion
amyloid
amylin
what is amylin
this is a amyloid polypeptide that is released from beta cells along with insulin and help to inhibit glucagon secretion and delay gastic eating
histology of type 1 diabetes
insulitis (infiltrate of T cells in the islet)
describe the effects of insulin on adipose tissue
striated muscle
liver
increase in glucose uptake in striated muscle like the heaty and in adipose tissue
increases protein sythesis increases fat synthesis (lipogenlysis) glcogen synthesis
decreases gluconeogensis in the liver
insulin is an _ hormone
anabolic
causes complex molecules to form from simpler ones
what type of fat is associated with obesity
white adipose
brown adipose increases glucose uptake/utilization
what are the 3 p’s of diabetes
how do they occur
polyuria- glucose in pee, water follows it creating an osmotic diuresis
polydipsia- urine water loss + increased blood glucose depeltes intracellular water and triggers thrist receptors
polyphagia- type 1 and later type 2; no insulin and there is fat/muscle breakdown
diabetic ketoacidosis is seen in _ and is severe _ def
type 1 diabetes
insulin
what causes DKA
what is released? what does this do
stress like infection or trauma
epinephrine is release and increased glucagon and blcoks insulin action
pathogensis of DKA
no insulin causes peripheral glucose to not be utilized
liver breaks down glycogen to create more glucose
fat is broken down to FFA and are metabolized by the liver to form acidotic ketone bodies
ketones and glucose spill into the urine and cause osmotic diuresis causing severe dhydration and ketocidosis
symptoms of DKA
fatigue, can lead to coma, fruity breath, deep labored breathing
what causes the fruity breath in DKA
ketone metabolism and acetone formation
ketones end up in the urine and a _ test can detect them, confirmatory tests involve checking the urine for?
nitroprusside
beta-hydroxyurea
what causes kussmal breathing in DKA
the body attempts to neutralize the metabolic acidosis by exhaling off CO2
what is hyperosmolar nonketotic hyperglycemic syndrome
this is a complication of type 2 diabetes especially in the elderly where there is prolonged insulin deficiency
this causes increased hepatic gluconeogenis, and glycogenolysis causing really high glucose
glucose greater than 600
no ketone bodies
and severe dehydration
can cause AMS and coma
what is matuirty-onset diabetes of the young (MODY)
what does it resemble
this is a monogenic diabetes that affects glucokinase of the beta cell
it resembles T2DM
there are no autoantiboies and is nonketotic
what is glucosekinase
a rate limiting enxyme in oxidative glucose metabolism that leads to the secretion of insulin
during pregnancy early on there is an increase in _ sensitivity that allows for a reservoir of energy supply. Later on _ _ block the effects of insulin and create insulin resistance this is because they want glucose in the blood to be able to cross over to the baby
insulin
placental hormones
in pregnancy maternal weight gain or underlying risk factors can cause insulin resistance to precipiate a state of?
gestational diabetes
how does th ebaby appear in a person with gestational diabetes
macrosomia
difficult birth (shoulder dystocia_
c section
congenital malformations (still birth)
describe the pathogensis of hyperglycemia
glucose causes advanced glycation of end products. End products have a vast majority of effects that cause the endothelium to become activated and allow for athersclerosis and vascular damage to occur
what other pathways contibute to hyperglycemia effects other than the glycationof end products
polyol pathway- loss of antioxidant production
hexosamine pathway- increase in oxidative stress
activation of protein kinase c (PKC) - increases growth factors and procoagulant activity
advanced glycation end products produces
vascular damage and athersclerosis
major complications of diabetes
athersclerotic disease (MI, cerebral infacrt, PVD–>gangrene)
retinopathy/ocular
neuropathy/peripheral neuropathy
nephropathy- ateriorsclerosis, pyelonephritis
infections- UTI, dental carries, candida
what fungal infection is common in diabetes
candida
describe the macrovascular athersclerotic disease in diabetes
brain
kidney
bowel
heart
peripherally
brain: can cause hemmorage or stroke
kidney: can cause renal artery stenosis and activation of the RAS system
bowel: can cause mesenteric ischemia
heart: chronic heart disease, MI
peripherally: claudication and ganreenoug necrosis
diabetic retinopathy and occular pathology is common and causes _ loss and diminished _
it can be divided into proliferative and nonproliferative: what are these
it can also cause _ and _ (end stages)
vision
sight
proliferative: formation of new vessels on the retina
non proliferative: anurysems in small vells and microhemorrhage; lipid leak
cataracts and glaucoma
diabetic peripheral neuropathy is a _ , _ , _neuropthy
distal
symmetric
polyneuropathy
symptoms of diabeteic peripheral neuropathy
numbness
loss of pain sensation
diabetic peripheral neuropathy is in a _ and _ distibution
glove and stocking
one of thedirect affects of peripheral neuropathy is injury to the _
foot
loss of sensation in the foot can lead to _ and infection
trauma
peripheral vascular disease in the foot leads to decreased _ and a _ foot (ulceration)
healing
diabetic
inflammationof the bones of the foot in diabetic neuropathy can lead to severe deformity of _ and joint and leads to a _ foot ( midfoot collapse/rocker bottom)
bones
charcot foot
diabetes can cause _ kidney disease
chronic
symptoms of chronic kidney disease
extermity edema, puritis, hypertension, bone fractures ( decresed calcitriol) and hypocalcemia
encephalopathy
what are the three principal vascular lesions in diabetic kidney nephropathy? in diabetes
renal vascular lesions
pyelonephritis
golmerular lesions
what are the renal vascular lesions in diabetic kidney nephropathy
athersclerosis thar causes renal atery stenosis and hypertension
hyaline ateriorsclerosis: from chronic hypertension and diabetes ( nephroclerosis of the kidney giving a grnaular nodular apperance)
what infection is increased in the kidney in a diabetic patient
pyelonephritis
**fevers, chills, flank pain, hematuria
_ _ is strongly associated with diabetic induced pyelonephritis
papillary necrosis
what does a diabetic glomerulus look like?
diffuse mesanglial slcerosis (increase in mesangium)
capillary basement membrane thickening
and PAS stained nodules (large) kimmelstiel wilson
