Schuler- Pancreatic Pathology Flashcards
in the _____ state there is Low insulin / high glucagon
fasting
in the ____ state there is high insulin/low glucagon
fed state
either not enough insulin produced or end up with tissues insensitive with insulin secretion
diabetes
GLUT receptor on beta cell
GLUT2
what happens when glucose comes into beta cell
lots of ATP produced
K+ channel closes (no efflux)
Ca2+ influx
insulin secretion
____ phase of insulin secretion: insulin secretion in abundance in response to high blood glucose
fed state
1st
____ phase of insulin secretion: prolonged phase, largely independent of blood glucose
2nd
_____need glucose to survive to perform metabolic processes
tissues
DM - low insulin/ low C-peptide
type I DM
normal or high insulin and C-peptide
type 2 DM
low C-peptide / high insulin
Excessive exogenous insulin
high C-peptide / high insulin
Insulinoma
drug that increases tissue specific insulin sensitivity; and one of the mechanisms by which they do this is increasing the translocation of GLUT4 transporters to cell membrane
Metformin
glucose transporter found in kidneys
SGLT2
glucose transporter found in intestines
SGLT1
pancreatic beta cells have what 2 glucose transporters
GLUT1 and GLUT2
hepatocytes have what 2 glucose transporters
GLUT1 and GLUT2
CNS haas what glucose transporter
GLUT3
skeletal muscle, cardiac muscle, adipose tissue has what glucose transporter that is insulin-dependent
GLUT4
lipogenesis at adipose tissue and liver
glycogen synthesis at liver and muscle
(by what)
insulin
Secreted by GI tract due to a meal
Slows down gastric emptying, and gives body more time to use substrates (pt stays full longer)
why pts lose weight
And increases insulin sensitivity in target cells
GLP-1 (incretin) agonists
incretin effect is significantly blunted in type 2 DM, so administering exogenous _____ is incredibly helpful
GLP-1
abnormal glucose metabolism resulting in hyperglycemia and dyslipidemia
diabetes mellitus
million Americans age 18 and older had prediabetes & are at high risk for developing frank diabetes
96
older patients
low socioeconomic status
ethnic minorities
susceptible to diabetes
Renal threshold b/t 180-200; if surpasses _____, kidneys unable to keep glucose from spilling over into the urine; sequellae: glucose in urine and fluid follows; dehydrated patients
200
fasting plasma glucose > _____ for diagnosing diabetes
126
2 hour plasma glucose from oral glucose test > ______ to diagnose diabetes
200
A1C > _____% for diabetes
6.5
A1C of 5.7-6.5%
prediabetes
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ _____mg/dL to diagnose diabetes
200
prediabetes oral glucose tolerance test
140-199 mg/dL
Formed by covalent binding of glucose moieties to hemoglobin in red blood cells.
_____is an indirect measure of BG levels and can be impacted by factors that impact hemoglobin
provides measure of glycemic control over the past 3-4 months
A1C
beta cell destruction, usually leading to absolute insulin deficiency
type 1 diabetes
Absolute deficiency of insulin
Autoimmune beta cell destruction
type 1diabetes
Most common subtype of diabetes diagnosed in patients < 20 y.o.
type 1 DM
Autoimmune attack begins many years before disease becomes evident
type 1 DM
lots of cellular infiltrate in beta cells
type 1 DM
Autoimmune, genetic, environmental
causes of type 1 DM
suspected cause of type 1 DM in _______ is recent viral infection
children
Rare form of Type 1 DM:
Absolute deficiency of insulin
No evidence of autoimmune beta cell destruction
Idiopathic type 1 DM
small, atrophic, distorted islet cells
idiopathic type 1 diabetes
classic triad of polyuria, polydipsia, polyphagia
type 1 DM
pt who is 10 yrs old w/ no bed wetting is now peeing in his bed at night
type 1 DM
unknown etiology
90% of diabetic patients are this
combination of insulin secretory defect w/ insulin resistance (with insulin resistance happening first)
type 2 DM
Overweight kids and/or familial history of diabetes screen them at age 10 for what
type 2 DM
genetics
environmental
metabolic defects
causes of type 2 DM
_____ causes muscle tissue to upregulate GLUT4 transporters; first line treatment for diabetes
exercise
Over-eating, obesity, inactivity, smoking
major causes of type 2 DM
how does obesity cause type 2 DM
central adipocity
fat cells release adipokines, FFAs, inflammatory cytokines
oxidative stress
insulin resistance in target tissues
rare form of diabetes, But these are single gene defects either in beta cell function or insulin action; something that they are born with; usually identified fairly early
monogenic diabetes
number 1 drug cause of iatrogenic diabetes; these patients will get central adiposity
glucocorticoids
these drugs can also result in hyperglycemia
atypical antipsychotics (mental health drugs)
state of increased insulin resistance superimposed on an already existing state of beta cell dysfunction or loss
gestational diabetes
risk factors for
gestational diabetes
If ______ is untreated: babies will have higher birth weight, mother can have preeclampsia, and low blood sugar
gestational diabetes
glucose tolerance test to check for gestational diabetes b/t what weeks
20-28
intermediate stages in the disease processes but not quite disease
prediabetes
_____ is major risk factor for CV events, dyslipidemias, and diabetes
obesity
Fasting plasma glucose between 100 and 125 mg/dL (not diagnostic)
prediabetes
2-hour plasma glucose between 140 – 199 mg/dL following a 75 –gm glucose OGTT
prediabetes
(HbA1C) level between 5.7% & 6.4%
prediabetes
basically, screen every _____ patient for diabetes
overweight or obese
most important contributor to insulin resistance
obesity
failure of target tissues to respond to insulin
insulin resistance
state of obesity results in _______ leading to insulin resistance
oxidative stress
Severe acute metabolic complication of DM (more common and severe in type 1 DM)
Diabetic Ketoacidosis (DKA)
Precipitating factors: failure to take insulin (most common); stressors – intercurrent infections, illness, trauma
DKA
stressors associated with release of epinephrine (blocks insulin release) cause this
DKA
Insulin deficiency + glucagon excess exacerbates hyperglycemia (blood glucose levels in 250 – 600 mg/dL range)
DKA
comes into ED w/ altered mental state, dehydrated
kids been wetting bed
Kussmahl breathing
”fruit-loopy” kind of smell to their breath
DKA
in DKA, ______oxidized in liver to ketone bodies (acetoacetic acid & beta-hydroxybutyric acid) which build up in blood (ketonemia) and urine (ketonuria)
free fatty acids
Dehydration compromises urinary excretion of ketone bodies, resulting in systemic metabolic _____
ketoacidosis
Absence of _____; unable to use glucose; brain needs fuel
ketogenic machinery kicks in and goes int overdrive
pt gets dehydrated due to excretion of ketone bodies and glucose
insulin
Can result in coma and death
Trying to blow out the acid (CO2) —-Kussmaul breathing
DKA
Seen in type 2 DM
Due to severe dehydration resulting in sustained osmotic diuresis associated with hyperglycemia
hyperosmolar hyperosmotic syndrome (HHS)
Typically an older disabled diabetic unable to maintain adequate water intake; dehydration w/ impaired mental status
hyperosmolar hyperosmotic syndrome (HHS)
Most common acute metabolic complication in either type of diabetes
hypoglycemia
treat hypoglycemia by
giving glucose
Develop 15 – 20 years after onset of hyperglycemia
Responsible for majority of morbidity/mortality associated with type 1 and type 2 DM
late complications of DM
PERSISTENT HYPERGLYCEMIA “GLUCOTOXICITY”
oxidative stress causing high glucose state
At the end of the day, trying to maintain blood glucose at a good range and increase insulin____ at target tissues
sensitivity
chronic complication of DM with accelerated atherosclerosis of large and medium-sized muscular arteries
macrovascular disease (MI, stroke, gangrene)
chronic complication of DM resulting in capillary dysfunction in target organs due to deposition of excess basement membrane material and synthesis of extracellular matrix
microvascular disease
diabetic retinopathy (retina)
diabetic nephropathy (kidneys)
diabetic neuropathy (peripheral nerve)
examples of microvascular disease as chronic complication of DM
_______involving the aorta, large- and medium-sized arteries
Coronary artery atherosclerosis and myocardial infarction
Most common cause of death in diabetics
Type 2 DM often accompanied by HTN and dyslipidemia
accelerated atherosclerosis
atherosclerosis
atherosclerosis
which vessel occluded
left anterior descending
Vascular lesion also associated with HTN; not specific for DM
More prevalent and severe in DM
Amorphous, hyaline thickening of the walls of arterioles causing luminal narrowing
hyaline arteriolosclerosis
hyaline arteriolosclerosis
vision changes and foamy urine
diabetic microangiopathy
diabetic microangiopathy
_____lesions seen in diabetic nephropathy
glomerular
glomerular lesions seen in diabetic nephropathy
Renal artery atherosclerosis & hyaline
arteriolosclerosis seen in diabetic_____
nephropathy
_____ is also seen in diabetic nephropathy that deals with infection from bladder up to kidneys
pyelonephritis
cellular infiltrare in kidney
acute pyelonephritis
Leading cause of end-stage renal disease in the U.S.
diabetic nephropathy
acquired opacification of the lens
cataracts
Most common cause of blindness in the U.S. in adults aged 20 – 74
diabetic retinopathy
increased intraocular pressure resulting in damage to the optic nerve
glaucoma
cataract
retinal blood vessel walls weaken; deals with HTN
nonproliferative diabetic retinopathy
new blood vessels growing into retina where they shouldn’t be
proliferative retinopathy
neurovascular glaucoma
Distal, ascending, symmetric sensorimotor polyneuropathy “stocking and glove” distribution involving hands and feet
diabetic neuropathy
Abnormal feeling in hands and feet (due to peripheral nerves not getting blood flow they need from capillary beds); getting enough that the tissue is not becoming gangrenous
diabetic neuropathy
Loss of pain sensation, numbness, difficulty with balance; Alternatively may have burning, prickling pain, tingling, aching in extremities
diabetic neuropathy
footdrop is diagnostic for what
untreated diabetes
Bowel, bladder, sexual dysfunction, footdrop
diabetic neuropathy
long term diabetes changes _____ function increasing susceptibility to infections
neutrophil
______ renal infection
candida
can be seen in pt in DKA; unconscious
Mucormycosis
