Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrine > Dagogo-Jack - Diabetes/Hyper and HypoNA Pathophys > Flashcards

Dagogo-Jack - Diabetes/Hyper and HypoNA Pathophys Flashcards

1
Q

What hormones are produced and released from the pancreas (in order of prevalence)? From what cells?

A
  • Insulin (beta cells)
  • Glucagon (alpha cells)
  • Somatostatin (delta cells)
  • Pancreatic polypeptide (gamma/PP/F cells)
  • Grehlin (epsilon cells)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is C-peptide so important?

A
  • Will not see it in the blood unless insulin was secreted, so it is a SURROGATE MEASURE of endogenous insulin release
  • 90-min 1/2-life (as opposed to 3-5 min 1/2-life of insulin), so there is time to measure this
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the phases of insulin secretion?

A
  • Blood glucose is the primary endogenous secretagogue
  • There are 2 phases of insulin excretion
    1. First phase is only about 3-10 minutes
    2. As glucose continues to enter the system, more insulin is synthesized and secreted (phase 2)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the molecular process for insulin secretion?

A
  • Glucokinase: glu to glu-6-phosphate -> TCA -> ATP
  • K(ATP) channel responds to fluxes in the ATP/ADP balance
  • When closed, Ca channels open, allowing for influx of Ca from the plasma into the beta cell
  • Ca-calmodulin complex triggers degranulation of insulin, and secretion into the blood stream
  • De novo transcription of insulin gene if glucose continues to enter the cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the most important anti-ketotic hormone? Why is this important?

A
  • Insulin is the most important anti-ketotic hormone
  • Without it, there is a risk of diabetic ketoacidosis (from lipid breakdown for energy in the absence of insulin) -> T1D
  • T2D typically protected from ketogenesis, but it can occur
    1. If someone has had diabetes for many years, they may be on low end of insulin reserve, and have a higher risk of DKA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the testing criteria for dx of prediabetes and diabetes?

A
  • A1C:
    1. <5.7% normal
    2. 5.7-6.4% prediabetes
    3. >6.5% diabetes
  • Fasting glucose levels used to capture most cases; this is the best possible chance to “pass” the test
  • Patient must be symptomatic to dx them on one, random blood glucose test over 200 (this is called opportunistic diagnosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How long are people typically prediabetic? Why is this important?

A
  • Most people spend a long time in an intermediate state between normal and diabetes —> often unrecognized until they become diabetic and symptomatic
  • Window of opportunity for prevention because people with prediabetes can stop progression via lifestyle changes
    1. Can even reverse this trend back to NORMAL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is an OGTT?

A
  • 75-g of glucose given to pt, then 2-hr levels drawn for dx purposes
  • Tests under provocative conditions tend to have better yield than tests done under basal conditions, so you may do this on a patient with a family history who comes back with a FPG of 120
  • Higher yield in people with higher risk: elderly, family history, history of high fasting glucose values, etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is HbA1C? How can it vary? Why does it matter?

A
  • Free glucose can be attached to amino terminal of hemoglobin (via NON-ENZYMATIC glycosylation)
    1. Estimate of diabetes progression in the last 120 days (3 months)
  • This measurement trumps daily measure of blood glucose because patients can “prepare” themselves for the doctor’s visit —> can be almost uninformative
  • Fn3K deglycation possible, so A1c is a balance b/t glycosylation and deglycation
  • Ethnic variation in glycosylation process, so A1c may vary according to race (even at same glucose level)
    1. These minor differences are usually not that important, but can be problematic for dx -> if borderline A1c, do blood glucose to verify before dx, especially if the patient is a minority
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does the 50% concordance in T1D twin studies mean?

A

Suggests an environmental role in the disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does the stepwise progression of T1D look like?

A
  • Begins with environmental triggers and genetic predisposure
  • Islet Abs: GAD, ICA, IAA, ZnT8
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What genetic factors are implicated in T1D?

A
  • HLA gene on chromosome 6
    1. DR3/4 in 95% of Europeans (coexpressed in 60%)
    2. DR2/DR2 protective
    3. DQ beta chain: Neg/Neg - full susceptibility
    a. Pos/Pos - full protection (also DQ7)
    b. Neg/Pos - 10% susceptibility
    4. DR4/DR4 overrides protective DQ alleles
    5. DQ8 (DQw3.2) - primary susceptibility
  • T1D 10x more prevalent in N. European descent
    1. In contrast, T2D more common in minorities
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is genetics involved in T2D?

A
  • 80% concordance in twin studies
  • However, leading gene still only account for 7% of variability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the progression of T2D (glucose, insulin graphs).

A
  • Resistance, followed by progressive dysfunction of pancreatic beta-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is insulin sensitivity?

A
  • Reflection of ability of insulin to:
    1. Stimulate glucose utilization in muscle and adipose
    2. Suppress glucose production in the liver
    3. INH lipolysis and stimulate lipogenesis
    4. INH proteolysis and stimulate protein synthesis
    5. INH ketogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the major risk factors for insulin resistance?

A
  • Majority of insulin resistance acquired via obesity and abdominal fat
  • Genetics
  • Age
  • Ethnicity
  • Obesity, overeating, inactivity, meds, others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does the acute insulin response in diabetics compare to controls (image)?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How are post-prandial glucose, insulin, and glucagon levels abnormal in diabetics compared to controls?

A
  • High glucose
  • Little to no insulin response
  • Glucagon stays high
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does GLP-1 do?

A
  • Secreted upon ingestion of food, and:
    1. DEC post-prandial glucagon secretion (reducing hepatic glucose output)
    2. Reduces gastric emptying
    3. INC glucose-dependent insulin secretion
    4. Stimulates satiety in brain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does SGLT-2 expression vary in diabetics?

A

Increased expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the products and pathology of the neurohypophysis?

A
  • Posterior pituitary
  • Products: ADH (vasopressin), Oxytocin, Neurophysins
  • Pathology: Diabetes insipidus (CDI), SIADH
22
Q

What are the half-lifes and neurohypophysial binding proteins for ADH and Oxytocin (image)?

A
  • Neurophysins are carrier proteins
23
Q

What are the factors regulating vasopressin release?

A
  • OSMOTIC:
    1. Stimulatory solutes: Na+, mannitol, urea
    2. Non-stimulatory solutes: glucose
  • NON-OSMOTIC:
    1. Hemodynamic: hypotension, hypovolemia
    2. N/V
    3. Hypoglycemia
    4. Renin-angiotensin
    5. Pain, stress, emotion
24
Q

What is going to cause a more extreme vasopressin response - volume or osmotic changes?

A
  • Higher response of vasopressin release to volume changes than with osmotic changes
  • Scale is COMPLETELY DIFFERENT (this same graph for osmolality only goes up to 25pg/mL ADH)
  • This isn’t only about retaining water, but also about constricting the vessels, which is very important in a patient who is bleeding
  • Skin will be cold and clammy because it is peripheral and sacrificed to maintain blood flow to the brain and other vital organs
25
Q

What are some of the dangers of hypernatremia and hyponatremia?

A
  • Can die in your sleep with severe hypernatremia due to tissue collapse (fluid moves into the blood due to hyperosmotic nature)
  • Hyponatremia: seizures and other CNS problems.
26
Q

What are the 2 main types of ADH receptors? Where are they?

A
  • Vasopressin: spasticity via V1 receptors and ADH effect via V2 receptors in the renal tubules
27
Q

What is synthetic oxytocin used for? Any concerns with its use?

A
  • Synthetic oxytocin can be used to induce labor (by stimulating uterine contraction), but can produce measurable and significant ADH effect when administered this way (temporary effect while drip is hanging)
  • Oxytocin can do some of the things ADH can do, but only at very high, extra-physiologic concentrations
28
Q

How do osmotic changes affect ADH release? What is the normal osmotic range in health?

A
29
Q

What are some effective measures to INC serum sodium in euvolemic pt with hyponatremia?

A
  • Restriction of fluid intake to 1000mL/day
  • Treatment with Conivaptan (vasopressin V2 receptor antagonist)
  • Note: infusion w/3% NaCl too dangerous and demeclocycline use outdated
30
Q

How does vasopressin INC renal water reabsorption (molecular level)?

A
  • INC aquaporins in apical membrane in collecting duct cells
  • V2 (previous slide) is a GCPR that works via adenylyl cyclase and cAMP -> VAPTANS can block the V2 receptor (good for CHF, nephrotic syndrome, SIADH).
  • AQP2 is the workhorse in the signal transduction mechanism
  • Excessive ADH activity in some pregnant women too
31
Q

What is the chemical structure of the aquaporins?

A
  • 6 transmembrane alpha-helices arranged in a right-handed bundle, with amino and carboxyl termini on the cytoplasmic surface of the membrane
  • Amino and carboxyl halves of the sequence show strong similarity to each other
  • Also five interhelical loop regions (A – E) that form the EC and cytoplasmic vestibules
32
Q

What is the main difference between endocrine and exocrine glands?

A
  • Endocrine glands do NOT have ducts (unlike exocrine glands), but rather release their contents directly into the blood
33
Q

What is the key mediator of ADH action? What are some examples of its down- and upregulation?

A
  • Vasopressin regulates water permeability of the kidney collecting duct by trafficking of AQP2 from IC vesicles to apical plasma membrane
  • Lack of function AQP2 in primary form of diabetes insipidus
  • DEC expression of AQP2 in several diseases assoc with urinary concentrating defects, like acquired nephrogenic DI, postobstructive polyuria (dramatic INC of urinary output after relief of urinary tract obstruction), and acute/chronic renal failure
  • In contrast, AQP2 levels are INC in conditions assoc with water retention: CHF, pregnancy, SIADH, suggesting a role for AQP2 in the devo of water retention
34
Q

Where is oxytocin?

A

􏰈- Nonapeptide found in the magnocellular neurons of the hypothalamic PVN, SON

􏰈- Also in smaller cells scattered around various parts of the brain

35
Q

What factors regulate oxytocin release?

A
  • Physiological regulation largely unknown
  • Suckling
  • Pregnancy and parturition
  • Osmotic factors
  • Hemodynamic factors
36
Q

How is oxytocin associated with human behavior?

A
  • Non-social: learning, INC anxiety, feeding, pain perception
  • Social: memory, attachment, sexual behavior, bonding/trust, and aggression
  • Might be involved in etiology of disorders of aberrant social interactions, such as autism and schizophrenia
  • Emerging functions (social affiliation, reproduction, bonding) are teleologically consistent with survival and propagation of the species
37
Q

What is the daily fluid balance (image)?

A
  • 60% comes in as water, and 60% goes out through the urine
38
Q

EC sodium? Renal tubular handling of Na?

A
  • Predominant EC cation: 136-145mEq/L
  • Pairs w/Cl-, HCO3- to neutralize charge
  • Most important ion in WATER BALANCE
  • Renal tubular reabsorption regulated by:
    1. Renin-Angiotensin-Aldosterone system: Na UP, K down via aldosterone
    2. Atrial Natriuretic Peptide (ANP): endogenous anti-CHF activated by atrial stretch —> diuresis
    3. SGLT: sodium-glucose co-transport proteins in the kidney
39
Q

What are the 3 types of hypernatremia?

A

􏰉- Hypovolemic: high urine output and Na+ excretion

  1. Increase in ANP is a potential cause of the loss of volume and Na
  2. With significant volume loss, orthostatic hypotension

􏰉- Hypervolemic: edema states (nephrotic syndr, CHF, cirrhosis)

  1. Water intoxication

􏰉- Euvolemic: ADH-mediated water retention, i.e., SIADH

40
Q

What is the clinical presentation of hyponatremia?

A
  • ACUTE (<24 hours)
    1. Early (Na <125mmol/L): N/V, headache
    2. Later (Na <120mmol/L: seizure, coma, respiratory arrest
  • CHRONIC (>48 hours): lethargy, confusion, muscle cramps, neuro impairment
41
Q

What is SIADH? Causes?

A
  • Syndrome of inappropriate anti-diuresis: hypo-Na+ with low pOsm
    1. uOsm > pOsm: low Na with urine osmolality higher than plasma osmolality —> WRONG
    2. Urine Na+ > 20mmol/L
    3. No edema, renal/endocrine disease, drugs
  • Causes:
    1. Paraneoplastic
    2. Trauma
    3. CVA (cerebrovascular accident: stroke)
    4. Infection
    5. Drugs: psychotropic, anti-cancer
42
Q

What are some non-pharma causes of SIADH?

A
  • TUMORS: carcinoma, thymoma, lymphoma, leukemia, sarcoma, mesothelioma
  • CNS DISORDERS: meningitis, encephalitis, head trauma, brain abscess, brain tumor, stroke, Guillan-Barre
  • RESPIRATORY: pneumonia, TB, empyema, pneumothorax, asthma, intermittent positive pressure ventilation (IPPV)
  • Note: infections/drugs in head and chest known to mysteriously cause SIADH (see the trend above)
43
Q

What are some pharma and miscellaneous causes of SIADH?

A
  • MEDS: vasopressin, oxytocin, vincristin, vinblastin, carbamazapine, thiazides, MAOIs, phenothiazines, nicotine
  • MISCELLANEOUS: acute psychosis, acute intermittent pophyria (porphyrin accumulations), post-operative period, hypothyroidism, glucocorticoid deficiency, idiopathic
  • Hypothyroidism leads to impaired free water clearance bc cortisol required to enhance free water clearance -> can lead to hyponatremia (which can appear like SIADH)
44
Q

How can you diagnose SIADH?

A
  • Hypotonic (hypoosmolar) hyponatremia
  • Urine Osm > Plasma Osm
  • Normal renal, adrenal, pituitary
  • High urine Na+, 24-hr urine

-

45
Q

What is the treatment for SIADH?

A
  • Remove underlying cause
  • Fluid restriction (preferred)
  • Block renal tubule response: demeclocycline (can cause teeth to yellow), lithium, or vaptans (V2 antagonists)
  • Hypertonic saline (risky): osmotic demyelination in the brain
  • NOTE: won’t be tested over this, except maybe Vaptans
46
Q

What is hypernatremia? Etiology?

A
  • Plasma Na+ > 145 mEq/L bc INC Na+, or DEC H2O
    1. Water moves from ICF to ECF
    2. Cellular dehydration: thirst, lethargy, irritability, seizures, fever, oliguria
  • Etiology: pure water depletion via central or nephrogenic DI
    1. Sodium excess: salt poisoning (PO or IV)
    2. Water depletion exceeding Na depletion: diarrhea, vomiting, DEC fluid intake
    3. Pharma agents: LITHIUM, Cyclophosphamide, Cisplatin
47
Q

What is the differential for DI?

A
  • Central DI: vasopressin deficiency
  • Nephrogenic DI: vasopressin resistance
  • Psychogenic: primary polydipsia
  • High urine output (6-10L per day) -> first thing to think about is DM (look for glucose in the urine)
48
Q

What are some of the causes of central DI?

A
  • FAMILIAL: isolated defect or in assoc with DM, optic atrophy, nerve deafness, bladder and ureter atonia (DIDMOAD syndrome)
  • ACQUIRED: idiopathic (about 50% of pts), trauma (head injury, sx in hypothalamic-pituitary region)
  • FUNCTIONAL: pregnancy
  • RARE: tumor (pituitary macroadenoma, metastases, craniopharyngioma)
    1. Granuloma: sarcoid, eosinophil granuloma
    2. Infection: pyogenic or tuberculous basal meningitis, encephalitis
    3. Vascular: peripartum hypotension, aneurysm
    4. External irradiation
49
Q

What are some tests you can do for DI?

A
  • Serum electrolytes, CBC, etc.
  • Plasma and urine osmolality
  • Water deprivation test
  • MRI of pituitary stalk
  • Plasma AVP (not routine)
50
Q

How do you do a water deprivation test?

A
  • Complete fluid restriction from midnight
  • No cigarette smoking
  • Hourly urine volume, osmolality, body wt.
  • Measure plasma osmolality when Uosm plateaus
  • Administer subcut. aqueous vasopressin, 5 units
  • Check urine osmolality 30 min and 60 min later
  • Compare maximum urine osmolality before and after vasopressin
51
Q

How do you interpret the results of the water deprivation test?

A
  • Max Uosm after vasopressin vs. max Uosm before vasopressin
  • >50% = central D.I.
  • <50% -> nephrogenic D.I. or psychogenic

Endocrine (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions