Endo Patho Flashcards
What is the exocrine role of the pancreas
Secretes digestive enzymes into duodenum
what is the endocrine role of the pancreas
secretes insulin(60%), glucagon(25%), and somatostatin(10%) into the blood from pancreatic islet cells
what are pancreatic Acinar cells and what do they secrete?
exocrine cells that secrete pancreatic enzymes
Amylase: carb breakdown
Lipase: lipid breakdown
DNA-ase: nucleic acid breakdown
RNA-ase: nucleic acid breakdown
Zymogens: Trypsinogen Chymotrypsinogen, Procarboxypeptidase A, B
what is the role of zymogens
enzymes that have no activity until they are cleaved (won’t destroy the pancreas)
how is insulin affected by dec liver function
insulin is degraded by insulinase which is produced in the liver. dec liver function=inc insulin half life
what is proinsulin
=insulin+C-peptide. It is the storage form of insulin. 5-10% of secreted product is in proinsulin form.
what is the half lives of C-peptide and insulin and how does this affect lab results
C-Peptide= hours
insulin= 6min
Check C-peptide levels to see if insulin is being released bc insulin doesn’t last as long.
how does insulin affect glucose, FFA, and AA
storage hormone changing glucose to glycogen, FFA to Triglycerides, and AA to proteins. It inhibits the reverse process. This causes cell growth and differentiation.
what is GLUT4
GLUT4 is the insulin-regulated glucose transporter found in adipose tissues and striated muscle
what is GLUT1. What is the effect from blocking it?
Glu transporter in GI and kidneys. Doesn’t require insulin to absorb glu.
Blocking= dec blood glu but causes diarrhea
what is GLUT2? What is the effect from blocking it?
found in prox segment in kidney. Also doesn’t require insulin to reabsorb glu from urine(up to 180).
Blocking= dec blood glu without GI SE
what is the pathway of Glu causing insulin release in B cells
GLUT2 transports Glu into B cells= mitochondria produces ATP= inhib sulfonylurea receptor(K+ channel)=cell membrane depolarization= opens Ca channel= Ca influx= stimulates Ca dependent insulin release
how do sulfonylurea drugs work
block K+ channel= inc insulin release
what is glycogenesis
glu to glycongen
what is insulins effect in muscle tissue
Increases glucose and amino acid uptake Stimulates Glycogenesis: glucose to glycogen Lipogenesis: glucose to triacylglycerol Protein synthesis: amino acids to protein
Inhibits
Gluconeogenesis: protein/lipids to glucose
Glycogenolysis: glycogen to glucose
Ketogenesis(lipolysis): lipids to ketones
Proteolysis: proteins to amino acids
what is insulins effect in the hepatic tissue
Increases glucose uptake Stimulates Glycogenesis: glucose to glycogen Lipogenesis: glucose to triacylglycerol Protein synthesis: amino acids to protein
Inhibits
Gluconeogenesis: protein/lipids to glucose
Glycogenolysis: glycogen to glucose
Ketogenesis(lipolysis): lipids to ketones
what is insulins effect in adipose tissue
Increases glucose uptake Stimulates Lipogenesis: glucose to triacylglycerol Inhibits Ketogenesis(lipolysis): lipids to ketones
what plasma glu level stimulates insulin release
> 80
at what plasma glu level is max insulin release
> 200
what inhibits insulin secretion
fasting, exercise, sympathetic activity/Alpha adrenergic stimulation(norepi, epi)
what stimulates insulin secretion
Glu, AA, FFA, gastro-intestinal hormones, neural influence
what gastro-intestinal hormones stimulate insulin secretion
Glucagon-like peptide 1 (GLP-1)
Gastric inhibitory polypeptide (GIP)
Secretin
what neural influences stimulate insulin secretion
PNS Stimulation
SNS via beta adrenergic(alpha cells predominate)
what problems might B-blockers cause in DM
beta adrenergic nerves stimulate insulin release. Blocking this can inc blood glu
what is glucagon’s effect
opposite of insulin
what stimulates glucagon secretion
hypoglycemia, AAs, Fasting, exercise, sympathetic B-adrenergic stimulation(norepi, epi)
what inhibits glucagon effects
glucose, insulin, FFAs, alpha-adrenergic stimulation
why does inc sympathetic B-adrenergic stimulation cause secretion of both insulin and glucagon?
need glucagon to inc blood glu and need insulin to inc metabolism
why does AAs cause secretion of both insulin and glucagon?
it allows for protein synthesis to occur while maintaining blood glu levels after high protein and low carb meals
what are normal, impaired glucose tolerance, and DM ranges for fasting plasma glu
normal 125
what are normal, impaired glucose tolerance, and DM ranges for oral glu test post 2hrs
normal 200
what are normal, impaired glucose tolerance, and DM ranges for A1C
normal 6.5%
what is the genetic component of DM1
95% of Caucasians have HLA-DR3 or HLA-DR4 with 40% having both
Insulin gene with variable number of tandem repeats in promoter
Monozygotic twins: 30%-50% Concordance
what is the genetic component of DM2
Genetic, but diff. from Type 1
>1/3rd have at least 1 parent with Type 2
Monozygotic twins: 100% concordance for Type 2 DM
Inheritance patter complex: multiple interacting susceptibility genes.
what is the autoimmune component of DM1
Post viral infection: mumps, rubella, coxsackieB, cytomegalovirus
T –cell response
Antibodies to beta cells
what is the autoimmune component of DM2
There is no autoimmune component to DM2
what is Maturity Onset diabetes of the young (MODY)
young pts develop DM2 from Mutations in a variety of genes (not from obesity) especially glucokinase mutation
primary beta cell defects
what is Maternally inherited diabetes and deafness caused from
microsomal DNA mutations
what causes gestational DM
either too much or increased sensitivity to human placental lactogen which is a protein in the mother that casues a rise in BS
when/how do you test for gestational DM
oral glu challenge test in 3rd semester
what is the rule of 1/3s with gestational DM
1/3 keep DM2 post delivery
1/3 have inc risk of DM2 post delivery
1/3 do not have inc risk of DM2 post delivery
what are the components of metabolic syndrome
Obesity (abdominal) Insulin resistance Fasting Hyperglycemia Increased lipids Hypertension
what is the pathogenesis of DM1
T-Lymphocytes reacting against poorly defined beta cell antigens
Inflammatory infiltrate, chronic, i.e., “INSULITIS”
what is the pathogenesis of DM2
INSULIN RESISTANCE
Beta cells UN-able to adapt to the “long term demands of insulin resistance”
Accumulation of amyloid protein
what is insulitits
inflammation of the islets of Langerhans of the pancreas
how does amyloidosis affect the pancreas
destroys the pancreatic islet in DM2
what % of beta cells are destroyed before manifestation of DM1 Sx
90%
how does DM inc risk for infection
Due to:
Impaired senses
Tissue hypoxia
Pathogens proliferate well in glucose
Decreased delivery of WBC’s
Altered WBC function
where are common infection locations due to DM
SKIN Lungs -TUBERCULOSIS -PNEUMONIA Kidneys -PYELONEPHRITIS Multiple locations -CANDIDA
what are the most common islet cell tumors? What others can occur?
Beta cells INSULINOMAS (NOT rare)
Alpha cells GLUCAGONOMAS (rare)
Delta cells SOMATOSTATINOMAS (rare)
what are gastrinomas
a gastrin-secreting tumor that can occur in the pancreas, although it is most commonly found in the duodenum. They produce ZOLLINGER-ELLISON SYNDROME, consisting of increased acid and ulcers
what are acute complications of DM
Hypoglycemia
Diabetic ketoacidosis (DKA)
Hyperosmolar Hyperglycemic NonKetotic Coma (HHNKC)
what are chronic complications of DM
Macrovascular Disease: atherosclerosis -CAD -CVA Microvascular Disease -Kidney: nephropathy -Retina: retinopathy -Nerves: neuropathy Immune -infections
what are hypoglycemic levels in newborns and adults? Why are newborns lower?
adults=<35
Newborns can use other sources besides glu for energy in the brain
what can cause hypoglycemia
Too much insulin
Decrease caloric intake
Exercise
Medications
what medication has a high risk of hypoglycemia
Sulfonylurea- may cause too much insulin to be released
how does hypoglycemia affect the nervous system
mainly affects the SNS
- tachy
- diaphoresis
- tremors
- pallor
- anxiety
what are the cellular manifestations of hypoglycemia
- HA
- dizziness
- irritability
- fatigue
- confusion
- visual changes
- hunger
- Sz
- coma
what is AKDA?
increase blood glucose with hormonal shift to antagonize insulin
9% mortality
what is the most common precipitating factor of DKA and how does it elevate BS?
illness/stress=inc cortisol= inc insulin resistance=inc glucagon and cortisol production= mobilize stored nutrients= further inc BS
what causes a well controlled DM1 to get DKA
inc cortisol= inc insulin resistance
what BS levels correspond to trace and 1+ urine dipstick glu levels
trace=100mg/dl
1+= 250mg/dl
how does inc release of glucagon, epi, GH, cortisol in DKA lead to coma
1) =inc FFA in blood= ketone body formation= metabolic acidosis= CNS depressant
2) =inc glycogenolysis=hyperglycemia= glycosuria= polyuria= dehydration= hyperosmolarity= CNS depressant
at what BS levels can DKA induce coma in DM1
300-400 due to acidity and osmolarity changes
at what BS levels can DKA induce coma in DM2
600-800 due to osmolarity changes
why is IV insulin given in DKA
dehydration would dec absorption of subq insulin
why is K+ falsely elevated in DKA
During DKA, there is inc H+ uptake into RBC by kicking out K+ creating false elevated K+ in serum. As you tx acidity, K+ will return into the RBC. Also insulin causes K+ to go into cells independent of H/K pump
What are the 3 main focuses of DKA tx?
fluids, K+, and insulin
How are fluids used in DKA tx
1) always start with NS (to prevent neuro swelling=diabetic neuropathy).
2) Then check the corrected Na. If >135 give .45NS, if <200 give fluid with dextrose to prevent delayed insulin effect.
what type of pt do fluids need to be given cautiously to?
Cardiac Dz pts
What insulin dose is used for DKA tx?
0.1U/kg IV
what are the characteristics of HHNKC
Low levels of FFA, therefore, no ketones
Sufficient insulin:
Extremely high glucose levels & severe volume loss and dehydration.
what is the Tx for HHNKC
fluid replacement, K+, and insulin
what is the somogyi effect
seen in DM1
Nocturnal hypoglycemia: increase insulin sensitivity
Rebound hyperglycemia
Manifestations: nightmares and morning headaches
how does the dawn effect differ from somogyi effect
Also in DM1, but no hypoglycemia at night
what is the somogyi effect tx?
protein rich diet prior to bedtime
what is the protein glycation pathway in chronic DM
induced by chronic DM
Non-enzymatic glycosylation
Occurs in proportion to the severity of hyperglycemia
Advanced glycosylation consists of covalently bound glucose: leads to physical cross-linking of nearby proteins contributing to thickening of vascular basement membranes.
what is the aldose redcutase pathway in chronic DM
Glu enters cells and is converted to Sorbitol production
Binds to basement membrane around vessels and nerves
what is the protein kinase C activation pathway in chronic DM
Increased production of extracellular matrix and cytokines
Enhanced microvascular contractility & permeability
Proliferation of endothelial and smooth muscle cells
how does chronic DM cause macrovascular dz
glu sticks on inside of vessles which makes it easier for fats to stick and form plaques causing atherosclerosis.
how does improvement in A1C levels affect macrovascular outcomes in DM2
studies have shown it has not been effective
what signs of retinopathy are associated with chronic DM
Microaneurysms Areas of hemorrhage Cotton wool spots Hard exudates Venous beading Neovascularization Retinal detachment Vitreous detachment Pre retinal hemorrhage
what is the first stage of DM retinopathy
Nonproliferative retinopathy
Increased retinal capillary permeability, vein dilation, microaneurysm formation and superficial and deep hemorrhages
what is the second stage of DM retinopathy
Preproliferative retinopathy
Progressive retinal ischemia with areas of poor perfusion resulting in infarctions
what is the third stage of DM retinopathy
Proliferative retinopathy
Presence of neovascularization and fibrous tissue formation within the retinal or optic disc
May see retinal detachment or hemorrhage into the vitreous humor
how can DM cause serious visual loss
formation of exudates, edema or ischemia occurs nears the fovea.
what is renal hyaline arteriolosclerosis?
marked thickened afferent arteriole
what effect does chronic DM have on the kidneys
1-thickened glomerular basement membrane
2-thinning of cortical tissue
3-diffuse granular surface of kidneys
what are Kimmelstiel-Wilson(KW) Kidneys
nodular glomerulosclerosis from DM damage
what is the metabolic theory of DM neuropathy
neuropathy caused from production of sorbitol
what is the vascular theory of DM neuropathy
neuropathy caused from dec blood flow
what is the subclinical stage of DM neuropathy
slowed motor & sensory nerve conduction without manifestations
what is the clinical stage of DM neuropathy
Symptoms present
Sensory before motor, distal degeneration, unmyelinated neurons affected first
what effect does DM neuropathy have on the autonomics
dec GI motility
postural hypotension
