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Endocrinology > Pathophysiology 3 > Flashcards

Pathophysiology 3 Flashcards

1
Q

Major Cellular Level Players of Calcium Regulation?

A
  • Ca
  • Phosphorous
  • PTH
  • Vit D
  • FGF23
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2
Q

Minor Cellular level players of Ca regulation?

A
  • calcitonin
  • magnesium
  • acid/base (pH)
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3
Q

Major Tissue Level Players of Calcium Regulation?

A
  • parathyroid glands
  • gut
  • kidney
  • bone
  • liver
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4
Q

Minor Tissue level players of Ca regulation?

A

-skin

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5
Q

Total Body Calcium

A

~1kg

  • 99% in bone (hydrocyapatite)
  • 1% extracellular and soft tissues
  • 0.1% intracellular
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6
Q

Serum Calcium

A
  • 40% protein bound
  • 10% complexed (citrate or phosphate ions)
  • 50% ionized - free Ca that is bioavailable
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7
Q

What does low Ca do?

A

-stimulates release from parathyroid glands
Bone: increase Ca immobilization from bone
Kidney: Increase Calcium reabsorption from DCT
Intestines: with vit D, increase calcium absorption

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8
Q

What does Parathyroid Hormone do?

A

1) activates 1alpha-hydroxylase
2) stimulates reabsorption of Ca (distal nephron)
3) inactivates phosphate transporter (PCT)
- decrease type II Na*Pi transporter (inhibits phosphate reabsorption)

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9
Q

PTH

A

-84 aa peptide

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10
Q

Calcium-Sensing Receptor (CaSR)

A
  • senses Ca2+ level
  • found in parathyroid, kidney, C cells thyroid, bone
  • a member of GPCR family
  • stimulating the receptor results in a intra-cellular cascade to reduce PTH secretion
    inc. Ca - calcimimetics - dec. PTH
    dec. Ca - calcilytics - inc. PTH
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11
Q

PTH Dependent Hypercalcemia

A
  • Hyperparathyroidism (primary/tertiary)
  • Familial hypocalciuric hypercalcemia
  • Medication-induced (Li or HCTZ-mediated)
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12
Q

PTH Independent Hypercalcemia

A
  • Tumor induced (PTHrP or bone metastases)
  • Granulomatous diseases (TB), sarcoidosis, lymphoma inc. 1,25 vit D
  • Multiple myeloma
  • Hyperthyroidism/adrenal failure
  • Immobilization
  • Medication-induced: vit D toxicity, vit A, milk-alkali)
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13
Q

Primary Hyperparathyroidism

A

-80-85% adenoma
-15% hyperplasia (MEN1, MEN2A, HPT-Jaw Tumor Syndrome, familial HPT)
-W>H), sex (F>M)
Unknown Etiology
Serendipity Stones Moans Groans Bones
abdominals psychic

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14
Q

Symptoms in Primary Hyperparathyroidism

A

Majority Asymptomatic

  • fatigue/weakness
  • musculoskeletal pain
  • polydipsia/polyuria
  • constipation
  • anorexia/nausea/dyspepsia
  • pruritus
  • depression/memory loss
  • renal failure/kidney stones
  • osteoporosis/fracture
  • HTN
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15
Q

Primary HPT Work up

A

Biochemical: Ca, Albumin (ionized Ca), PTH, 25-OH Vit D, 24 hr urine Ca (to differentiate from FHH)
Imaging: Thyroid US & 99Tc-sestamibi scan-local
DXA

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16
Q

Management of Primary HPT

A

parathyroidectomy

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17
Q

Management of Primary HPT

A

Conservative

  • adequate hydration
  • use of bisphosphonates in patients with osteoporosis
  • maintenance of Vit D status (20-30ng/mL)
  • cinacalcet has been approved by FDA for those who do not qualify for surgery and have moderate hypercalcemia (Ca>12.5)
  • annual follow up: Ca/PTH, renal function, DXA
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18
Q

Familial Hypocalciuric Hypercalcemia

A

1) inactivating mutation of CaSR, 100% penetrance
2) Mildly inc. serum Ca, high-normal/mildly inc. PTH, hypocalciuria
3) asymptomatic
4) Work up: Serum Ca, PTH, 24 hr. urine calcium (<50-100 mg/24hr) Can also ask relatives to check serum Ca, genetic testing
5) no treatment is indicated

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19
Q

Tertiary Hyperparathyroidism

A
  • occurs in the face of long standing secondary hyperparathyroidism
  • parathyroid glands develop hyperplasia due to chronic low Ca and/or high Phosphorous levels
  • at 1 point, these glands become autonomous in the setting of end-stage renal disease or post-kidney transplant
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20
Q

Hypercalcemia of malignancy

A

-Clinical Presentation: consistent with signs and symptoms of hypercalcemia and potential diagnosis of malignancy
-polyuria, dehydration, confusion, abdominal and musculoskeletal pains, fatigue, nausea/vomiting
-weight loss, pulmonary symptoms, lymphadenopathy, history of cancer, Anemia, abnormal chest X-ray
Etiology: breast, lung, lymphoma, thyroid, kidney, prostate, multiple myeloma, pancreas
-breast and squamous cell carcinoma more common
-PTH level will be suppressed

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21
Q

Hypercalcemia can occur in malignancy without increase in PTHrP

A
  • bony metastases can increase Ca levels
  • humoral factors (cytokines, TNFa) can activate osteoclasts
  • multiple myeloma can cause significant bone destruction resulting in hypercalcemia
22
Q

Initial Treatment of Acute Hypercalcemia

A
  • address volume status
  • saline diuresis +/- furosemide (only after corrected volume)
  • calcitonin IM/SC (4-6 IU/kg q6-12 hrs) 3-4 days
  • Bisphosphonates (Pamidronate IV over 4hrs for 2-3 weeks) or Zoledronic acid IV over 15min
  • Glucocorticoids (useful in myeloma, granulomatous disease, Vit D toxicity)
  • Phosphate (rarely used, caution elevated Ca X Phos product)
  • Dialysis
23
Q

Major Causes of Secondary PTH Elevation

A

1) Hypocalcemia
2) Hyperphosphatemia
3) Vit D Deficiency

24
Q

Approach to patient with Secondary Hyperparathyroidism

A

1) Symptoms are non-specific and likely related to underlying disease causing elevated PTH but not due to PTH itself
2) Evaluate key elements of the Ca axis: serum PTH, Calcium (with albumin), Phosphorous, Creatinine, Vit D (do not collect 24-hr urine for Ca)
3) No indications for imaging studies if calcium is normal
4) Treat underlying reason (make sure vit. D is always replete)

25
Q

Vitamine D Deficiency

A

1) Severe vit D deficiency is rare
2) Presenting complains in mild/moderate vit. D deficiency are very non-specific: musculoskeletal pains, fatigue
3) 50% of patients with osetoporosis have vit. D deficiency
4) Vit. D replacement (>800 units/day) showed
~20% reduction in risk or fractures
-benefits of vit D replacement for prevention of cancer, diabetes mellitus, infections, hypertension are controversial
-J-shaped association between mortality and vit D levels

26
Q

Clinical Signs of Hypoclacemia

A
  • agitation
  • hyperreflexia
  • convulsions
  • hypertension
  • long QT
27
Q

Hypoparathyroidism (low PTH)

A

-primary process as low PTH decreases Ca

post-thyroidectomy
idiopathic-antibodies to PTH
autoimmune
parathyroid agenesis eg: DiGeorge syndrome
hypomagnesaemia, hypermagnesemia, hyperphosphatemia

28
Q

Hyperparathyrodism (high PTH)

A

-secondary process or when PTH increases due to low calcium from other resons

renal failure
vit D deficiency
vit D or PTH resistance syndromes

29
Q

Acute Pancreatitis

A

-free fatty acids chelate Ca

30
Q

Massive Transfusion

A

-infusion of citrate will complex with Ca leading to decreased ionized Ca

31
Q

Tumor Lysis Syndrome or Rhabdomyolysis

A

-phosphate release binds to ionized Ca

32
Q

Severe Sepsis

A

Cytokines mediated

-hypocalcemia

33
Q

Medications that cause hypocalcemia?

A
  • phosphate

- bisphosphonates

34
Q

Hungry Bone Syndrome

A

-hypocalcemia

35
Q

Work up of Hypocalcemia

A 
PTH is low
-Hypoparathyroidism 
-Magnesium Deficiency
-Phosphate Excess
PTH is high
-severe vit D deficiency
-renal failure
-vit D resistance or PTH resistance
36
Q

Pseudohypoparathyroidism

A
  • idiopathic inherited forms of PTH resistance
  • elevated PTH (1000s), hypocalcaemia, hyperphosphatemia
  • short stature, rounded face, foreshortened 4th metacarpals, obesity (albright’s hereditary osetodystrophy)
  • variability in AHO or PTH renal resistance, subclassified
37
Q

Pseudohypoparathyroidism Molecular Defect

A

inability of PTH to stimulate intracellular signaling events (cAMP pathway) due to mutation in Gsalpha subunit or elements downstream to cAMP signaling

38
Q

Hypocalcaemia Treatment

A 
Acute: always correct Mg if low
-Ca gluconate (93mg elemental Ca/10ml)
-1-2ampules over ~10-20min
-0.5-2.0mg/kg/hr of elemental Ca IV
Long Term:
-oral Ca salts (3g a day)
-Vit D (ergocalciferol/cholecalcirerol) -effective only if PTH is present
-Calcitroil 0.5-1.0mcg/day

-Hydrochlorothiazide - increases reabsorption of Ca in distal tubule

39
Q

MEN (multiple endocrine neoplasia)

A

1) AD - germline or sporadic mutations (2nd hit)
2) Different Penetrance (varying phenotype)
3) Benign & Malignant
4) Functionally Active and Inactive

40
Q

Tumors in MEN

A

1) Parathyroid (primary HPT) 80-95%
2) Pancreas (insulinoma, gastrinoma, VIPoma) 50%
3) Pituitary (prolactinoma, Cushing’s disease, acromegaly) 25%

41
Q

Epidemelogy of MEN

A

-hypercalcemia due to HPT by age 40
-Pituitary tumors age 38
-Pancreatic tumors:
Insulinoma age 25
Gastrinoma age 35

42
Q

Parathyrooidectomy in patients with PHPT and Gastrinoma

A

-improves hypercalcemia and decreases gastrin

43
Q

MEN2A

A
  • 1/30,000, any age, more adults, 80% of all MEN2
    1) medullary thyroid carcinoma - almost 100%
    2) Pheochromocytoma - 40%
    3) Primary HPT - 25%
44
Q

MEN2AB

A
  • 1/30,000, early onset, 5% of all MEN2
    1) MEdullary thyroid carcinoma - 100% more malignant
    2) Mucosal Neuromas - 100%
    3) Marfanoid habitus - 50%
    4) Pheochromocytoma - 50%
45
Q

Clinical Features of MEN2B

A
  • Mucosal neuromas

- marfanoid habitus

46
Q

Screening of MEN2B: Biochemical

A
  • index patient, complete screening by testing function of other endocrine glands of MEN
  • in first deg. relative initiate screening to identify hyperfunction of an endocrine gland known to be a part of MEN
47
Q

Screening of MEN2B: Genetic

A
  • index pat. screen for most prevalent genetic mutation for this type of MEN (genetic counseling)
  • in first degree relatives, genetic screening once mutation is confirmed in index patient
  • children are most vulnerable group
48
Q

Clinical Features of MEN2B

A
  • Mucosal neuromas

- marfanoid habitus

49
Q

Screening of MEN2B: Biochemical

A
  • index patient, complete screening by testing function of other endocrine glands of MEN
  • in first deg. relative initiate screening to identify hyperfunction of an endocrine gland known to be a part of MEN
50
Q

Screening of MEN2B: Genetic

A
  • index pat. screen for most prevalent genetic mutation for this type of MEN (genetic counseling)
  • in first degree relatives, genetic screening once mutation is confirmed in index patient
  • children are most vulnerable group

Endocrinology (15 decks)

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