Case One Review

1
Case One - Review
2
What are rales? What does their presence
indicate?

• Rales clicking, rattling, or crackling noises
  heard during inspiration.
• Due to "popping open" of small airways and
  alveoli collapsed by fluid, exudate, or lack of
  aeration during expiration.
• Suggests
• Pneumonia,
• Atelectasis,
• Pulmonary fibrosis,
• Acute bronchitis, or
• Bronchiectasis.
• Pulmonary edema secondary to left-sided
  congestive heart failure can also cause rales.

• History and Physical Exam
• A 60 y.o. ?
• Chief complaint fever and productive cough for
  approximately two months
• Fatigue and low back pain
• Physical Exam
• Alert ?, oriented
• BP 120/90
• HR 90 bpm RR 23
• Temp. 102.2 oF
• Bilateral rales
• Rest of exam - unremarkable

3
Radiology
Normal Flat Plate
Patient On Admission
Bilateral infiltrates
4
CBC

• Nucleated RBC (NRBCs) 5
• Immature RBCs not normally seen in peripheral
  blood beyond neonatal period.
• Appearance in peripheral blood of children
  and adults signifies bone marrow damage or stress
  and potentially serious underlying disease.
• Disorders that disrupt bone marrow
  architecture (e.g. fibrosis, metastatic tumors),
  an increased rate of erythropoiesis (e.g.
  hemolytic anemia), and in megaloblastic and
  dyserythropoietic disorders.

• Normocytic, normochromic anemia
• MCV, MCH, MCHC all normal
• Reticulocyte normal
• Malignancy
• Myeloma
• Chronic Disease

5
Iron Deficiency Anemia Longstanding

• Most common anemia
• Low or depleted iron stores
• Develops slowly months as iron stores are
  depleted ? microcytic - hypochromic anemia
• In men and post-menopausal women often indicates
  GI tract bleeding
• Monthly menstrual bleeding - in premenopausal
  women
• Symptoms
• Fatigue and diminished capability to perform hard
  labor
• Lack of circulating hemoglobin however, out of
  proportion to the degree of anemia and probably
  are due to a depletion of proteins that require
  iron as a part of their structure

• Proof
• Bone Marrow smear
• Microcytosis apparent in the smear long before
  the MCV is decreased
• Platelets usually are increased in this disorder.
  
• ?Serum iron,? total iron-binding capacity (TIBC),
  and ? serum ferritin
• A low serum iron and ferritin with an elevated
  TIBC are diagnostic of iron deficiency.
• While a low serum ferritin is virtually
  diagnostic of iron deficiency, a normal serum
  ferritin can be seen in patients who are
  deficient in iron and have coexistent diseases
  (hepatitis, anemia of chronic disorders).
• ? serum Ferritin
• liver damage,
• inflammation
• infection, or cancer
• http//www.emedicine.com/med/fulltopic/topic1188.h
  tm

6
Given the bilateral infiltrate, what is the
significance of the increased numbers of bands?

• Seen in
• Acute infection
• Metaboloc acidosis
• Necrosis myocardial infarct. malignant tumors
• Blood disease
• hemolytic crises,
• severe blood loss
• chronic  granulocytic leukemia,

• Likely an infectious process
• WBC elevated
• Band cells increased
• Unilobed and two lobed nucleus predominate

7
CHEMISTRY

• Significance of both CR and BUN being elevated by
  roughly the same amount?
• Kidney problems
• ??Ca
• gt 98 - A parathyroid problem
• lt 1 of cases due to cancer...
• Multiple Myeloma
• Lung (squamous cell CA - not all lung cancers)
• Breast Cancer (advanced disease)
• Kidney Cancer
• Squamous Cell Cancer of the Head and Neck

8
BUN ELEVATED

• Nearly all primary renal diseases increase BUN
• Glomerulonephritis
• Pyelonephritis
• Acute tubular necrosis
• Urinary obstruction

• BUT THERE ARE OTHER IMPORTANT DISEASES THAT ALSO
  INCREASE BUN

9
BUN Blood Urea Nitrogen

• Source breakdown of blood, muscle, and protein
• Excreted Entirely by kidney
• Level of BUN is a function of both synthesis and
  excretion

• High
• Renal disease
• Urinary Tract Obstr.
• Dehydration
• CHF
• GI bleeding
• Starvation
• Shock
• Low
• liver disease
• malnutrition

10
CREATININE ELEVATED

• Production of Cr depends only on muscle mass,
  rarely fluctuates
• Entirely excreted by kidney
• ONLY renal disorders will affect CR levels

• BUNCr ratio 201
• If BUN gtgtCr think PRE-RENAL dehydration,
  malnutrition, CHF, hepatic failure
• If BUN CR are ?think RENAL

11
URIC ACID

• Excreted primarily through the kidneys (75)
• More than 90 of patients with elevated BUN and
  serum creatinine also have increased uric acid.
• Associated with
• Chronic renal disease
• Acute renal failure
• Severely decreased renal blood flow
• Other conditions include drugs (diuretics
  particularly thiazides), ketoacidosis of diabetes
  or starvation, lactic acidosis, toxemia of
  pregnancy and hypothyroidism. Gout
• Most common reason for an elevation in uric acid
  in hospitalized patients is prerenal azotemia.
• Urea increases faster than creatinine
• Size matters! Urea is small and readily
  reabsorbed by the tubules. So if it gets
  filtered is still can be reabsorbed

12
Electrolytes
13
Culture results

• Gram positive cocci in pairs and chains
• Consistent with Streptococcus pneumoniae

14
Two weeks later

• Fever gone, chest clear
• Back pain worse

15
HEMATOLOGY 2 weeks later
16
CHEMISTRY 2 Weeks later
17
Urinalysis
18
Proteinuria

• Normally no protein in the urine.
• Glomerulus prevents protein from spilling into
  the urine
• Source of proteins albumin and globulin from
  plasma
• Losses gt 2000mg/24 hours in adults (3 -
  dipstick) usually indicates a glomerular
  etiology.
• Urine dipstick DOES NOT detect Bence Jones
  Protein of Multiple Myeloma ? 24 hr. urine

19
Multiple Myeloma

• What is it Multiple myeloma - cancer of plasma
  cells
• Expansion of a single line of plasma cells that
  replaces normal bone marrow and produce
  monoclonal immunoglobulins
• Plasma cells develop from B lymphocytes ?produce
  antibodies that fight infection
• Over years tumor erodes the inside of the bone,
  producing holes in the bones (called "lytic"
  lesions).
• Since the malignant cells are clones they act
  exactly alike and produce the same antibody
  molecules ?
• Diagnosis Suspected because of one or more of the
  following
• Bone pain in which lytic lesions are discovered
  on routine skeletal films
• An increased total serum protein concentration
  and/or the presence of a monoclonal protein in
  the urine or serum
• Systemic signs or symptoms suggestive of
  malignancy, such as unexplained anemia
• Hypercalcemia is either symptomatic or discovered
  incidentally. Nearly half of all people with
  myeloma have hypercalcemia at some stage in
  disease
• Acute renal failure with a bland urinalysis or
  rarely the nephrotic syndrome due to concurrent
  primary amyloidosis
• Diagnostic Criteria
• Presence of an M-protein in serum and/or urine
• Presence of clonal bone marrow plasma cells or
  plasmacytoma (discrete, solitary mass of
  neoplastic monoclonal plasma cells in either bone
  or soft tissue )
• http//www.emedicine.com/med/topic1521.htm

20
Bence Jones Protein

• First tumor marker 1848!
• Small proteins (light chain immunoglobulin)
  present in urine in Multiple Myeloma and a few
  other diseases
• Waldenstrom's macroglobulinemia, some lymphomas
  and leukemias, osteogenic sarcoma,
  cryoglobulinemia, malignant B-cell disease,
  amyloidosis, light chain disease, and cancer that
  has spread to bone.
• Made by plasma cells
• 24 hr urine, heat to 140 ºF (preciptiates),
  further heating dissolves, cool -gt preciptitate

21
Renal Disorders in MM

• Myeloma cells produce large numbers of proteins.
• Fragmentation of some of these immunoglobulins
  produces a special protein (ie, Bence-Jones
  protein).
• This protein, as well as others produced by the
  malignant plasma cells, MAY BE deposited in the
  kidney tubules.
• The proteinemia in myeloma often exceeds the
  resorptive ability of the kidney, resulting in
  proteinuria
• ? spillage of Bence-Jones protein.
• Amyloidosis is a frequent finding (8-15) in
  patients with myeloma and further contributes to
  parenchymal dysfunction.
• Calculi are often found because of elevated uric
  acid and calcium levels.
• All of these factors can eventually result in
  renal failure and death.

22
Peripheral Blood Smear
Patient
Normal
Rouleaux formation correlates with an increased
concentration of serum monoclonal proteins.
Rouleaux may be seen as an artifact in the
thicker portions of blood smears.
Normochromic,normocytic anemia
Rouleaux
23
Skull x-rays

• Randomly distributed, rounded, punched out lytic
  lesions throughout the skull. Multiple myeloma
  could also resemble metastatic breast carcinoma.
  Treated breast carcinoma, however, often appears
  sclerotic rather than lytic.

24
Staging Multiple Myeloma
25
Serum Protein Electrophoresis

• Note sharp peak in the gamma region indicative of
  a monoclonal protein

26
Risk Factors for Multiple Myeloma

• Age and Gender
• 1 are diagnosed in people lt40
• 2/3 are diagnosed in people gt65
• Men are 50 more likely to develop MM than woman
• Race
• 2X as common among black Americans as white
  Americans.

• Occupational Exposure
• Petroleum-related industries MAY be at higher
  risk
• Obesity
• Other Plasma Cell Diseases
• Many with MGUS or solitary plasmacytoma will
  eventually develop MM