Rr-Symptoms - Unintentional Weight Loss

Front 1

Unintentional weight loss characteristics

Back 1

Loss of 10 pounds or > 5% of baseline body weight in 6-12 months.

First establish if the weight loss is intentional

Inquire if the patient's food intake is less, or the same/increased

Front 2

Differential of weight loss

Back 2

DECREASED BODY MASS

Depression
Endocrinopathy
Cancer
Renal Failure
Enteric
Access to Food
Systemic inflammatory disease
Eating difficulty
Diabetes Mellitus

Bulimia & Anorexia
Opportunistic Infection
Dementia
Yucky food

Medication side effects
Aging
Systemic chronic disease
Schizophrenia/psychosis

Front 3

Lymphoma

Back 3

malignancy of white blood cells arising in the lymph nodes.

Front 4

Leukemia

Back 4

Lymphoid neoplasms with widespread involvement of bone marrow. Tumor cells are usually found in the peripheral blood

Front 5

Non-hodgkin Lymphoma

Back 5

- Burkitt's: African pt w/ jaw mass
- Diffuse large B cell
- Mantle Cell t(11:14) deactivation of cyclin D regulatory gene, CD5+, poor prognosis

Follicular t(14;18) bcl-2 expression, which inhibits apoptosis, indolent course but difficult to cure

Lymphoblastic T cell, children, mediastinal mass

Cutaneous T cell, mycosis fungoides

Adult T cell with HTLV-1 infection

Marginal Cell MALToma H pylori associated

Front 6

Burkitt's Lymphoma

Back 6

Highly aggressive B cell non-hodgkin lymphoma "starry sky" histology sheets of lymphocytes with interspersed macrophages
Occurs in children and young adults sporadic, or associated with HIV

Front 7

Burkitt's Lymphoma is associated with?

Back 7

In Africa associated with Ebstein Barr Virus and presents as maxillary/mandibular mass

Front 8

Genes of Burkitt's Lymphoma

Back 8

c-MYC gene on chromosome 8 t(8;14) places c-MYC proto-oncogene adjustment to immunoglobulin heavy chain locus on 14w overexpression of the transcription factor c-MYC that leads to increased cell-growth CD20, CD10, and BCL-6.

Front 9

Treatment of Burkitt's Lymphoma may lead to?

Back 9

Treatment may lead to tumor lysis syndrome low phos, low calcium, increased uric acid, increased potassium and AKI, preventable w/ hydration and allopurinol.

Front 10

Back 10

Burkitt's Lymphoma

Front 11

B symptoms of Hodgkin's Lymphoma

Back 11

Wt loss, fever, night swears - patients sometimes itch, node doesn't hurt

Front 12

Cells of Hodgkin's Lymphoma

Back 12

Reed-Sternberg cells - formed from germinal B cell centers CD15+ CD30+

Front 13

Hodgkin's Lymphoma Treatment

Back 13

Curable, excision +XRT or advanced ABVD chemo adriamycin, bleomycin, vinblastine, dacarbazine

Front 14

Subtypes of Hodgkin's Lymphoma

Back 14

- Nodular sclerosis
- lymphocyte predominance
- lymphocyte rich
- lymphocyte depleted (HIV) or mixed cellularity (25% older patients with EBV)
- Prognosis better with more lymphocytes and less Reed Sternberg cells

Front 15

Back 15

Hodgkin's Reed Sternberg Cell characterized by large size, bilobed nucleus, and nucleolar inclusion bodies "owl's eyes"

Front 16

Vincristine: Mechanism

Back 16

M phase specific that blocks polymerization of microtubules so mitotic spindle cannot form

Front 17

Vincrisitne : Uses

Back 17

Acute leukemia, Hodkin's, WIlms tumor, choriocarcinoma

Front 18

Side Effects of Vinblastine

Back 18

Neuropathy peripheral neuritis, areflexia, paralytic ileus

Front 19

Part of MOPP regimen for Hodgkin Lymphoma

Back 19

Mustargen, oncovin, procarbazine, prednisone

Front 20

Signs and Symptoms for Leukemia

Back 20

Leukemia is unregulated growth of leukocytes in bone marrow so in addition to bone pain many symptoms are related to problems of production

There is decreased working WBCs (infections, esp cellulitis)

Decreased Hgb & HCT (fatigue, dyspnea on exertion, pallor on exams)

Decreased platelets (Bleeding gums, epistaxis, petechiae)

Leukemic infiltrates can occur in liver, spleen, and lymph nodes. Hepatosplenomegaly on exam

Front 21

CML Chronic Myelogenous Leukemia: Cytogenic analysis

Back 21

t(9;22) Philadelphia chromosome results BCR-ABL fusion gene, translocation of ABL proto-oncogene to BCR

Bcr-Abl fusion protein results in constitutively active Abl tyrosine kinase in the Ras/Raf/MEK/MAPK pathway which leads to inhibition of apoptosis and unregulated cell division.

Front 22

Age of onset of CML

Back 22

35-55

Front 23

Associated symptoms of CML

Back 23

Splenomegaly, hepatomegaly, lymphadenopathy

Front 24

Blood characteristics of CML

Back 24

Leukocytosis, normocytic to macrocytic anemia

Bone marrow is hypercellular

Front 25

Effect of CML on platelets

Back 25

Platelet derangement either thrombocytosis during active phase or thromobocytopenia in spent phase

Front 26

Histology of CML

Back 26

Promyelocytes, big cell and nuclei, coarse grains in cytoplasm, basophilic

Front 27

Hydroxyurea

Back 27

S phase specific agent binds ribonucleotide reductase and inhibits the formation of DNA

Used in melanoma, CML, and sickles cell disease

Front 28

Hydroxyurea : side effects

Back 28

nausea, vomiting, bone marrow supression

Front 29

Busulfan

Back 29

Cell cycle nonspecific agent - alkylating agent
Cross links DNA and RNA stranfs
Used in CML

Front 30

Side effects Busulfan

Back 30

Pulmonary fibrosis and hyperpigmentation

Front 31

Imantinib

Back 31

Highly specific Bcr-Abl tyrosine kinase competitive inhibitor

Blocks proliferation, induces apoptosis in BCR-ABL positive cell lines and fresh leukemic cells

Gleevec is well tolerated: side effect is fluid retnention

90% cytologic remission rate

Dasatinib is second line

Front 32

CML to Blast Crisis

Back 32

Progresses in 3-5 years to accelerated phase and then blast crisis, additional genetic abnormalities accumulate and lead to AML

Peripheral smear shows >20% blast cells

Front 33

Symptoms of AML

Back 33

- low platelets lead to epistaxis and petechiae
- bone pain
- anemia with dyspnea
- gingivial hyperplasia (leukemic invasion)
- leukemia cutis (skin infiltrates)
- cellulitis is common presentation due to neutropenia bc of replacement of mature WBCs with leukemic cells leading to infections
- Neurologic defects
- DIC (more often in AML)

Front 34

DIC

Back 34

Thrombohemorrhagic process with microthrombi throughout the body. Widespread activation of clotting leads to deficiency of clotting factors and leads to bleeding.
Consumes platelets so thrombocytopenia occur
Decreased fibrinogen as converted to fibrin
Increased D dimers (fibrin split products) - this is the most specific lab test due to activation of protein C and plasmin leading to fibrinolysis
Prolonged coagulation labs with increased bleeding time, increased PT and increased PTT

Occurs in the better prognosis AML t(15;17) which is FAB M3 acute promyelocytic leukemia because All-trans retinoic acid is effective treatment by inducing differentiation

Front 35

AML Characteristics

Back 35

60-65 years
Poor prognosis in contrast to ALL
Defect in maturation beyond myeloblast or promyelocyte state which appear on peripheral smear

Front 36

Stain for AML

Back 36

Periodic acid-Schidd stain PAS - (negative) which distinguished from ALL which occurs most often in children

Front 37

AML: microscopy

Back 37

Auer rods: peroxidase positive cytoplasmic inclusions in granulocytes and myeloblasts

Front 38

Back 38

Auer rods

Front 39

Genetics of Acute Promyelocytic Leukemia

Back 39

t(15;17) translocation is a feature of acute promyelocytic leukemia

All-trans retinoic acid for treatment, vitamin A induces differentiation

Release of Auer rods leads to DIC disseminated intravascular coagulation

Front 40

Methotrexate

Back 40

S phase specific antimetabolite - folic acid analog- decreases dTMP, decreases DNA and protein synthesis; immunosupressant

Front 41

Indication for Methotrexate

Back 41

AML, bone marrow transplant for abortion, ectopic pregnancy, rheumatoid arthritis and psoriasis

Front 42

Side effects of Methotrexate

Back 42

Oral and GI ulceration, megaloblastic anemia immunosuppression, thrombocytopenia, leukopenia, fibrotic lung disease, mucositis, hepatotoxicity

Front 43

Leucovorin "rescue"

Back 43

Given as adjuvant after treatment to reverse myelosuppression

Front 44

Cytarabine (ara-C)

Back 44

S phase specific antimetabolite, pyrimidine analog that inhibits DNA polymerase

Used in AML

Front 45

Side effects of cytarabine

Back 45

Leukopenia, thrombocytopenia, megaloblastic anemia

Front 46

Granulocyte Colony Stimulating Factor

Back 46

Aldesleukin human recombinant interleukin-2 can be used in AML

Filgramstim or Sargramostim granulocyte-macrophage stimulating factor for recovery of bone marrow during chemo induced neutropenia

Front 47

Graft vs. Host Disease

Back 47

- Caused by donor lymphocytes attacking recipient cells

- Seen in non-autologous bone marrow transplants

- Most common sites liver (elevated LFTS), skin (severe rash), and GI (watery diarrhea)

Front 48

ALL

Back 48

Acute Lymphoblastic Leukemia
<15
can spread to CNS and testes
t(12;21)
better prognosis but in general all variants very responsive to therapy

PAS periodic acid-Schiff stain +positive

Front 49

CLL

Back 49

Chronic Lymphocytic Leukemia/Small lymphocytic lymphoma
age >60
smudge cells
hepatosplenomegaly

Front 50

Hair cell leukemia

Back 50

Stains TRAP positive
mature B cell tumor in elderly

Front 51

Back 51

Hairy cell leukemia

Front 52

Back 52

Front 53

Back 53

Front 54

Symptoms of Hyperthyroidism

Back 54

1. Alertness, emotional lability, nervousness, irritability
2. Poor concentration
3.* muscular weakness, fatigability
4. palpitation
5. voracious appetite, weight loss*
6. increased frequency of bowel movements
7. heat intolerance

Front 55

Signs of hyperthyroidism

Back 55

1. Hyperkinesia, rapid speech
2. Proximal muscle weakness, fine tremor
3. Fine, moist skin; fine, abundant air; onycholysis (separation of nail from its bed); pretibial skin thickening
4. Lid lag, stare, chemoisis, periorbital edema, proptosis
5. Accentuated first heart sound, tachycardia, afib, widened pulse pressure, dyspnea

Front 56

Normal Thyroid Histology

Back 56

Front 57

Graves Disease

Back 57

Autoimmune
- diffuse involvement
- microscopic appearance
-- irregular follicles
-- scalloped colloid

Front 58

Back 58

CRH stimulates ACTH - stimulate adrenal gland to produce cortisol... stress axis can by physical stress, chemical stress, or many other stresses .

Front 59

Back 59

Cortisol and Circadian Rhythm

Front 60

Adrenal Insufficiency: Primary adrenal insufficiency:

Back 60

-destruction (usually irreversible) of the adrenal cortex (autoimmune; tuberculosis; adrenal hemorrhage)

Cortisol low; ACTH high (loss of negative feedback)

Aldosterone low; renin high (loss of negative feedback)

Front 61

Secondary Adrenal Insufficiency

Back 61

Chronically inadequate ACTH secretion resulting in loss of adrenocortical volume = adrenal atrophy

Cortisol low, ACTH inappropriately not increased

Aldosterone and renin : usually unaffected

Front 62

Signs and symptoms of adrenal insufficiency

Back 62

Fatigue, malaise, lack of energy

GI: nausea, vomiting, anorexia --> wt loss

Hypotension ---> dizziness, orthostasis

Increased skin pigmentation, salt craving (primary)


WEAKNESS, FATIGUE, ANOREXIA, WEIGHT-LOSS

Front 63

Histology and Physiology of the Adrenal Glands

Back 63

- Zona glomerulosa : Mineralocorticoids = "salt"
- Zona fasciculata : Glucocorticoids = "sugar"
- Zona reticularis : Estrogens and androgens = "Sex"

Front 64

Back 64

Front 65

histology of pituitary gland

Back 65

Anterior: secreting the horomones - acth, tsh etc.
made up of basophil and acidophil (primarily)

Front 66

Anterior Pituitary Gland Architecture (reticulin stain)

Back 66

Reticulin network around lobules of normal glands - if it's gone means that you're having a proliferation of cells w/o normal architecture - pituitary adenoma

Front 67

Back 67

Autoimmune disorder classically affecting young women during late pregnancy or in the early postpartum period, mimics adenoma on neuroimaging and shows sheets of cytologically bland pure lymphocytic infiltrates.

Front 68

Back 68

Front 69

Symptoms of hypercalcemia

Back 69

- Related to level and rate of change
- Fatigue, weakness
- Nausea, vomiting, constipation
- Anorexia
- Polyuria, polydipsia
- Dehydration
- Memory impairment
- Drowsiness, confusion, coma
- Most ambulatory patients - no clear symptoms

Front 70

Back 70

Front 71

What causes hypercalcemia

Back 71

Increase in PTH secretion
Primary hyperparathyroidism (usually a parathyroid adenoma)

Front 72

What does hypercalcemia result in?

Back 72

Suppression of PTH secretion
Vit D intoxication, hypercalcemia of malignancy (caused by PTHrp)

Front 73

Primary hyperparathyroidism

Back 73

Hypercalcemia; serum PTH inappropriately not suppresed (can have hypophosphatemia; high normal or increased calcium excreation)
- Sporadic (single and multiple gland disease, carcinoma)

Front 74

MENs associate with Primary hyperparathyroidism: MEN1

Back 74

parathyroid, pituitary, pancreatic islet

Front 75

MENs associate with Primary hyperparathyroidism: MEN2A

Back 75

Parathyroid, pheochromocytoma, medullary carcinoma of the thyroid

Front 76

MENs associate with Primary hyperparathyroidism: MEN2B

Back 76

Medullary carcinoma, pheochromocytoma, neuromas/ganglioneuromas

Front 77

PTH- Independent hypercalcemia : Malignancy

Back 77

Bone metastases, PTH-related protein, osteoclast activating factors, unregulated calcitriol production, true ectopic PTH

Calcitriol-mediated (granulomatous, inflammatory) (calcitriol = 1,25(OH)2D)

Front 78

Characteristics of normal parathyroid

Back 78

Yellow, brown ovoid nodule
30-45mg
Composed primarily of chief cells and some oxyphil cells
In adults there is a large amount of intervening stromal fat (30-70%)
Chief cells secrete parathyroid hormone

Front 79

Back 79

Normal Parathyroid Gland

Front 80

Back 80

Front 81

Parathyroid Adenoma

Back 81

Solitary nodule arising in a single parathyroid gland
0.5 - 5.0 grams
Other glands are either normal or atrophic
Composed of sheets of chief cells with decrease in stromal fat
Oxyphilic cells may also be present
May show a rim of normal parathyroid at the periphery

Front 82

Parathyroid Adenoma

Back 82

Front 83

How is Graves disease best rules out?

Back 83

By measuring a suppressed serum TSH (increase neg feedback inhibition of pituitary thyrotrophs)

Front 84

Hashimoto shows?

Back 84

Autoimmune condition
Show lymphocytic infiltration

Front 85

What does Graves show?

Back 85

Autoimmune condition
Irregular follicular borders
Scalloped colloid

Front 86

Adrenal Insufficiency

Back 86

An ambulatory patient is best rules out with an ACTCH stimulation test (primary AI - adrenal destroyed; secondary AI - adrenal atrophied)

Front 87

Adrenal cortical atrophy can be caused by

Back 87

increased glucocorticoids, pituitary dysfunction (sheehan, panhypopituitarism), Addision disease (autoimmune destruction)

Front 88

Mild hyperalcemia

Back 88

Requires evaluation for possible primary hyperparathyroidism

Front 89

Primary hyperparathyroidism

Back 89

PTH is usually in the upper part of the reference range or increased

Hypercalciuria may be present because the filtered load of calcium has exceeded the Tm for calcium in the kidney

Front 90

Most common cause of primary hyperparathyroidism

Back 90

Parathyroid adenoma