NSG 530 Advanced Pathophysiology Exam #2 Questions and Verified Detailed Answers; for Guaranteed Success -Wilkes University

Overview of the Blood

•Blood

•5000ml

•Plasma

•3000ml

Hematocrit defined

- % of RBCs

[higher value = higher viscosity = thicker blood)

- Example: Polycythemia may have Hct of 60-70%

Types of Blood Cells

- Erythrocytes [RBCs)

- Transport O2

- Small disc shape

- Lifespan = 120 days

- Carry Hgb [ferrous oxide, also an acid/base buffer)

- Made in the bone marrow - Iliac crest for sample in leukemia

[after age 20 in the vertebrae, sternum, ribs, iliac)

- Hgb Levels: 14-16g/dL in males / 12-14g/dl females

Cytic vs Chromic

Cytic = Size of RBCs

Chromic = Amount of Hgb

MCV and MCHC

MCV: Mean corpuscular volume - [average size rbc]

MCHC: normal Mean corpuscular Hgb concentration - [average amount of hemoglobin in the RBCs compared to the average size of the RBCs. The amount of hemoglobin that was there

Morphology Size or Erythrocyte Volume Cytic Values

- Normocytic: Normal RBC size

[MCV = 83-99)

- Microcytic: Small RBC size

[MCV = 50-82)

- Macrocytic: Large RBC size

[MCV is > 100)

Chromic Values

[Hgb content)

- Normochromic: Normal amount of Hgb [MCHC -Average amount of hemoglobin in the RBCs compared to the average size of the RBCs.

[MCHC = 32-36)

- Hypochromic: Low amount of Hgb

[MCHC is < 32)

- Hyperchromic: Increased amount of Hgb

[MCHC is > 36)

Leukocytes

[WBCs)

- Defend the body against foreign proteins

- Made in the bone marrow

- 9,000/mm^3

- CBC w/ Diff shows: Leukocytes broken down into:

Neutrophils, Basophils, PMNs [polymorphonulcear), Bands

Bands - {Infective process

-Immature Leukocytes

- Indicate an infective process

- Increase in bands = 12 to 20 or more = shift to the left indicating a bacterial infection

- If bands are not increased it is a shift to the right and a viral infection

Alterations of Leukocytes

Quantitative:

1. Bone marrow dysfunction

2. Premature destruction of cells

a. May originate in lymphoid organs secondary to infectious process

Leukocytosis equals increase WBC's

Leukopenia Equals decreased wbc's

Types of Leukocytes:

- Granular

- Categorized according to the presence or absence of granules in the cell cytoplasm

- *Granular Leukocytes*:

- PMNs - Polymorphonuclear leukocytes[2 or more lobes to the granular site)

- Neutrophils

- Eosinophils - Allergic reaction or parasites

- Basophils

Types of Leukocytes:

- Non-granular

*Non-granular* Leukocytes :

- Lymphocytes

- Monocytes

- platelets or thrombocytes

WBC Morphology/Fx

[Shape and function]

- Total WBC count increases with infection

- As % of 1 increases, the %s of the others will decrease

[shift in %) = Shift to the left or shift to the right

- Bands = immature neutrophils aka stabs

[German for rods due to shape)

WBC Morphology/Fx

- Bands being immature with infection there is an increase in production

= shift to the left

- Neutrophils = segs or polys = mature polymorphonuclearcytes and segmented

WBC's and bands

Should tell you right away that when you have an infection and the WBCs are called on to replicate and attend to this infection, that the faster they do it the more immature cells they have so the more bands produced.

How to tell if an infection is viral or bacterial?

- If there is a shift to the left [increase in bands) it is bacterial

- This is because of the way the differential used to be displayed [Shift to the left then you would see the WBCs going up, the bands going up, the neutrophils or segs rising as well and the other percentages going down [lymphocytes and monocytes in particular]

Response to infections

- Neutrophils are released

- Many are immature or "bands"

- "Shift to the left" indicating more bands = acute bacterial infection

- "Shift to the right" indicates a more viral infection

Platelets

- Small, round, colorless cells

- Made in the bone marrow

- Lifespan: 5 - 8 days

- Normal level: 150k - 300k

- Key substance for blood clotting

Pathology of Platelets

- Thrombocytopenia Purpura

Caused by: Viruses, radiation, and drugs

- Example = HELLP Syndrome:

[Hemolysis. Elevate Liver enzymes. Low Platelets)

Due to Hypertension,spilling proteins

Pathology of Platelets and pregnancy

- Seen in pregnant women

- The liver doesn't make platelets

- Delivery of the baby is the treatment

- C-section is the best way, To prevent mother from deteriorating into a DIC - risky due to low platelet count

Blood Proteins

- Albumin

- Normal range is 3-5

- Sponge Responsible for blood osmotic pressure

aka oncotic [pulling) force - Albumin and its presence in the bloodstream and with it , hydrostatic pressure and oncotic pressure functions and blood returns to the vascular tree.

- Assists with wound healing

Problems with low albumin levels

- Low albumin = low oncotic pressure = leakage of fluids into the interstitial space = ascites and edema of dependent extremities

- Albumin Usually

low albumin levels

- Decreased albumin is usually from decreased liver fx

- Reavis says that giving albumin IV does nothing because it doesn't stay in the vessels, it leaks out.

Reavis surgeon story about Albumin

- Liver CA pt had 19L of paracentesis fluid removed

- MD filtered it and put it back into the pt IV which caused a spike in albumin resulting in a spike in oncotic pressure resulting in a crisis and increased CVP

Blood Proteins

- Globulins

- Alpha

- Beta

- Gamma

[Part of the inflammatory / immune process)

- May be used to transport molecules

Anemias

- Not a disease

- Reduced number of RBCs or quality/quantity Hgb

- O2 carrying capacity of Hgb is reduced

S/S of Anemias

- Hypoxia

- Night cramps

- Angina

- Fatigue

- Weakness

S/S of Anemias continued

- Dyspnea with pallor

- Tachycardia, palpitations, systolic murmur, hypertrophy, HF

- Increased Epogen = bone pain and sternal tenderness

- Increased 2, 3, DPG = reduction in Hgb affinity for O2

What is the #1 Diff Dx for pt's c/o fatigue?

ANEMIA

Anemia Patho

- Defined as a Hgb less than 10

- Pernicious Anemia: = Lack of B12 and/or intrinsic factor)

- Hypoxia [rate of RBC production is increased by erythropoietin in response to this

- Bone Marrow suppression

due to CA, drugs, radiation, chemo)

- Disorders of hemostasis

- Disorders of Leukocytes

5 Classifications of Anemias by etiology

- Altered Hgb synthesis

- Altered DNA from deficient nutrients

- Stem Cell dysfunction

- Bone marrow infiltration

- RBC Destruction

Class of Anemia:

- Altered Hgb Synthesis

- IDA (Iron deficiency anemia)

- Thalassemia

- Anemia of chronic disease

Class of Anemia:

- Altered DNA from deficient nutrients

- Pernicious anemia

[B12)

Class of Anemia:

- Stem Cell dysfunction

- Aplastic anemia [cells not made at all)

- Myeloproliferative leukemia

Class of Anemia:

- Bone marrow infiltration

- CA

- Lymphoma

Class of Anemia:

- RBC / Erythrocyte Destruction

- Blood loss

- Hemolysis INTRAcorpuscular [cell itself)

- Hgb S [sickle cell)

- G6PD [Oxidation-Glucose-6-phosphate dehydrogenase deficiency)

- EXTRAcorpuscular [outside the cell)

- Immune mechanisms

- Infection

Red blood cells / glycolysis / ATP

How dependent the red blood cell is on ATP production from glycolysis - The glucose molecule through glycolysis you get this bisphosphoglycerate which is the precursor to the hemoglobin that is necessary for the red blood cell to function correctly.

Blood Loss Anemia

- Acute hypovolemia and shock usually

- Cells are normcytic and normochromic

- Low H&H

- Hypoxia causes and increase in RBC production

[compensatory mechanism - takes a while)

- H&H should return to normal in 3-4 weeks

Blood Loss Anemia - Causes:

- L&D [iron supps and prenatal vits help prevent this - In one month back to normal)

- Trauma

- Insidious loss due to ulcers or lesions

*According to Reavis, all pts of age or that are insidiously bleeding With a drop in hemoglobin are to have a colonoscopy to help prevent colon CA

Microcytic Anemia - small cell

MCV 52-82, MCHC 24-32 - Do not hold as much hemoglobin = low MCHC

Microcytic Anemias:

Seen in :

- IDA = Iron deficiency anemia

- Thalassemia

Microcytic Anemias:

- Thalassemia

- Genetic disorder passed on to children

- Recessive trait

- Minor: 2/4 alpha forming genes are defective

[both parents pass on to minor, child would present with major]

- Major: incompatible with life - all 4 alpha forming genes are defective - O2 cannot be released to the tissues

Causes of Microcytic Anemias

- Chronic Diseases:

- CRF [Chronic Renal Failure)

- DM

- RA

Diagnosis for Microcytic

[Small RBCs)

- Iron deficiency anemia

- Anemia of chronic disease

- Labs to help differentiate:

-a. Transferrin

- b. Serum Fe

- c. Ferritin

- d. TIBC

Pathology when the pt is Normocytic and Normochromic - Cell size normal / MCHC is normal

MCV 82-92, MCHC 32-36

- Hemorrhage - acute blood loss

- Hemolysis

- Chronic diseases [ draw TIBC [total iron binding capacity] low and ferritin rises = anemia of chronic disease that is early on

Anemia [aplastic and early iron deficiency]

- EARLY iron deficiency [transferrin rises [when iron stores in body are low] and ferritin falls[blood cell contains iron] =Iron deficiency anemia

- Aplastic Anemia - Cancer hypoplastic cell invading the bone marrow where red blood cells are made

Macrocytic Values

- Big RBCs

MCV > 100

MCHC > 36

3 Types of Macrocytic Anemias

- B12 deficiency

- Folic acid deficiency

- Antimetabolites

- Low B12: normal folate

- Must be used with Intrinsic factor which is missing from the stomach

- Low B12 and normal Folate

- Tx: B12 injections

- Folic acid deficiencies:

- Low folate

- Causes neural tube deficits

- Tx: Oral folic acid

Macrocytic Anemias - Antimetabolites

- Antimetabolites:

- Pernicious [destruction of parietal cells /Gastric mucosa = no production of intrinsic factor which absorbs B12)

- Tx: B12

Reavis pt story about B12

- Has a pt that comes in for B12 shots because it gives them more energy

- Insurance does not pay for this bc the pt lacks a dx of pernicious anemia

Etiology of B12 Deficiency

- Inadequate intake

- Decreased absorption

- Inadequate utilization

- Usually occurs in the 5th or 6th decade of life

Forms of B12 deficiency

- Pernicious

- Autoimmune disease producing autoantibodies to gastric parietal cells and their secretory produce [IF) - necessary for B12 absorption

- Crohn's disease

- Whipple's disease

- Sprue [Increased cases)

- Post Gastrectomy (B/c the parietal cells have been removed)

-Drugs / Chemotherapy

RDA [Recomm. Daily Allowance) of B12

- 2 micrograms/day

[avg person gets 3-9/day)

- Alcoholics are usually low in B12 because according to Reavis they only buy alcohol and not food so they have low dietary intake

S/S of B12 deficiency

1.* Smooth/beefy red tongue + atrophy on top [atrophic glossitis) - not tongue rugae

2. - Fatigue

3. - Malabsorption/diarrhea from megaloblastosis of epithelial cells of small intestine

4.- Paresthesia/numbness from peripheral neuropathy / lesions in posterior-lateral columns spinal cord/cerebrum)

S/S of B12 deficiency continued

5. Loss of vibratory and position sense

* a. Loss of Sensory ataxia

* b. Positive Romberg - balance test with eyes closed

* c. Weakness

* d. Spasticity

6. Cerebral manifestations:

-a. Personality changes and memory loss

-b. Psychosis

Folate Deficiency

- Etiology: Dietary deficits

- S/S: Similar to B12 but WITHOUT NEURO SYMPTOMS

- So fatigue

- Tx: PO Folic Acid

- Dietary counseling with foods high in folic acid

Foods high in Folic Acid

- Liver

- Wheat Bran

- Leafy Green Veggies

- Beans

- Grain

Diagnosis Folate Deficiency

•First draw a CBC with differential, peripheral smear

•Group according to red cell indices and blood smear results

•Macrocytic?

•Approach differentials B12? -Shilling test [confirms low level is result of intestinal malabsorption due to intrinsic factor deficiency)

Diagnosis Folate Deficiency

•Folate Deficiency

•Microcytic

•Differentiate IDA and Chronic Disease

•Transferrin, Serum FE, Ferritin, TIBC

Folate Normal Levels

- Adults: 2-20 ng/mL OR

4.5-45.3 nmol/L.

Hereditary Hemachromatosis (HH)

- Etiology [cause]

- Hereditary: autosomal RECESSIVE

- In general population: 0.3% - 0.5%,

but 11% are carriers

- Most common hematologic genetic disorder [in US)

- 1/10 Caucasians are carriers

*Body absorbs to much iron*

Hereditary Hemachromatosis (HH) -

- Etiology continued

- Males affected 5-10 times more than females

[iron loss during menses prevents it from showing up)

- First s/s usually appear after age 40

- Environmental factors may accelerate the process due to:

a. Iron rich diet, High intake of Vit C, Alcohol abuse

Reavis story about Hereditary Hemachromatosis [HH)

- Male pt in for annual check up

- Is a recovering alcoholic in rehab and takes megavitamins

- CBC showed an elevated Hgb

- Skin was sallow and yellow in appearance

Hereditary Hemachromatosis [HH) Patho

- Disorder of iron metabolism [IRON OVERLOAD)

- Increased intestinal iron absorption

- Deposited ino the liver, pancreas, heart, joints, pituitary gland and endocrine glands

- This causes progressive tissue damage and functional impairment

Hereditary Hemachromatosis (HH) Patho continued

Not on lecture

- Normally crypt cells have HFE protein that facilitates transferrin receptor dependent iron uptake

- Disorder in crypt cells of the duodenum

- HFE protein malfunctions cause relative iron deficiency = an increase in DMT-1

[Divalent metal iron transporter 1)

-Equals increase in intestinal absorption

S/S of Hereditary Hemachromatosis [HH)

- Fatigue

- Abdominal pain

- Arthralgia

- Weight loss

- Change in skin color [marked)

- Decreased libido

- Palpitations

- Menstrual changes

- Impotence [of both sexes according to Reavis)

- Cirrhosis

- Diabetes

Diagnosis of Hereditary Hemachromatosis (HH)

- Labs

-CBC with deifferential

- Elevated Transferrin saturation

- Elevated ferritin levels

* Fasting in the AM when levels are the highest

- Liver Bx [quantitative hepatic iron)

Treatment of Hereditary Hemachromatosis (HH)

- Early Dx and Tx prevent long-term complications

- Goal is to remove excess iron periodically through:

* Repeated phlebotomy - donate blood

*Most efficient and least expensive

Treatment of Hereditary Hemachromatosis (HH) cont

**a. Donate blood [1-2 pints weekly) 1 Pint = 473mL

until the levels decrease.

- Can take 2-3 years

* b. Maintenance is blood donation every 3-4 months

* Monitor transferrin sat & ferritin levels annually

Hereditary Hemachromatosis (HH)

- Dietary Changes

- Avoid large amounts of red meat [high in iron)

- Restrict iron supps or multivits high in iron

- No vit C supplements [< or = to 500mg/day)

- In absence of cirrhosis, alcohol intake in moderation

- No raw shellfish

- Black tea and grains help bind iron

[this plays a minor role)

Prognosis of Hereditary Hemachromatosis (HH)

- Liver / spleen decrease in size

- LFTs return to normal, but cirrhosis is irreversible

- Check for hepatocellular carcinoma

- Skin pigmentation decreases

- Cardiac dysfunction improves

- Diabetes may NOT improve, but disease progression may SLOW

- Arthralgia, impotence, menstrual problems may NOT improve

Increased Epogen =

- Increased bone pain

- Sternal tenderness

Causes of Leukocytosis - increased WBC's

- Infectious organisms

- Exercise

- Emotional changes

- Temp changes

- Anesthesia, surgery

- Pregnancy

- Drugs

- Hormones

- Toxins

Alterations of Leukocytes - can be quantitative

*Quantitative*

1. Bone marrow dysfunction

2.Premature destruction of cells

a. May originate in lymphoid organs secondary to infectious process

Leukocytosis is a defense mechanism...

- Absolute Leukocyte count that is HIGHER than normal

- Absolute neutrophil count is greater than 7500 - Neutrophils become so few that they cannot defend your body

Leukopenia

- Never normal or beneficial

- Defined as as an absolute blood cell count less than 4000 cells/mm3

Pathologic Leukocytosis

- From Malignancies

- Hematologic disorders such as Myelotic leukemia having an absolute neutrophil count greater 100,000/microliters which

* Increases the viscosity of the blood and the risk of thrombus formation

Neutropenia

- Defined as neutrophil count 200/microliter

Low count of Neutrophils which destroy bacteria.

Causes of Neutropenia

- Severe prolonged infection

- Aplastic anemia

- leukemia

- Drug or Toxin induced

- Starvation / anorexia nervosa

Neutropenia is a classic s/s of what?

Anorexia nervosa

Severe Neutropenia [Granulocytopenia or Agranulocytosis]

Called [Granulocytopenia or Agranulocytosis] which causes:

- Interference with hematopoiesis

- Increased cell destruction in circulation from:

a.Chemotherapeutic agents

b.Drugs: NSAIDS and anti-thyroid drugs

Agranulocytosis can be a complication of what?

Anti-thyroid medications

S/S of Severe Neutropenia

- Malaise

- Septicemia

- Fever

- Tachycardia

- Ulcerations in the mouth/colon

- Death if untreated

Eosinophilia

- Greater than 450/microliter

- Caused by:

- Allergic disorders

- Atopic dermatitis

- Eczema

- Pemphigus

- Scleroderma

- Parasitic infestation

1st thing to think about when you have a pt with watery diarrhea and Eosinophilia?

- Gastroenteritis from a parasitic infection

Basophilia

- Too many Basophils

- Response to inflammation/hypersensitivity

- Contain histamines

- Caused by:

- Myeloproliferative disorders like

- CML

- Meyloid metaplasia = basophilia

Basopenia

[*HASO*]

- Too few basophils

- Caused by:

- Hyperthyroidism

- Acute infection

- Long-term steroid therapy

- Ovulation and pregnancy

Lymphocytes and Infectious Mononucleosis

[Mono)

- Acute

- Self-limiting

- Neoplastic lymphoproliferative syndrome

- Infection of B lymphocytes

- From the EBV

- Etiology: viral transmission, oral/fecal

Lymphocytes and Infectious Mononucleosis

- Incubation period is 30-60 days

- Diagnosed with blood tests

- Monospot may be false positive)

- Heterophilic antibody test is the MOST

ACCURATE way to dx Mononucleosis - *HAT* test

Leukemia

- Clonal malignant disorder of blood / blood forming organs

- Accumulation of dysfunctional cells

- Loss of cell division regulation causing uncontrolled proliferation of leukocytes which:

- causes overcrowding of

bone marrow

- and decreased production and function of normal hematopoietic cell

4 Types of Leukemias

- (ALL): Acute Lymphocytic

- (AML): Acute Myelogenous

- (CLL): Chronic Lymphocytic

- (CML): Chronic Myelogenous

Classes of Leukemias

1. Acute or chronic comes as Undifferentiated or immature [blast) cells

2. *Myeloid or Lymphoid Leukemia arise from:

- 80% are from B cells

- 15% - 20% are from T cells

Acute Leukemias

- Usually seen in the neonate period

- Onset is abrupt

- Survival is short

Most common genetic error resulting in Leukemia

- Reciprocal translocation between chromosomes 9 and 22 (Philadelphia chromosome)

Chronic Leukemias

- Have mature cells, but they don't function normally

- Onset is gradual

- Survival is longer

ALL is most commonly seen in...

Kids

Clinical Manifestations of ALL - acute lymphocytic leukemia

Anemia

Bleeding

DIC

Infection

Weight loss

Bone pain

-Elevated uric acid [by product of protein catabolism, urate concentration secondary to dehydration caused by anorixa or fever and drug TX]

- TX: Chemotherapy, supportive TX, allopurinol for gout, bone marrow transplants

CML [Chronic Myelogenous Leukemia)

- Clonal, neoplastic expansion of multipotent myeloid stem cell [myeloproliferative disease) -NEB cells

Etiology - Philadelphia chromosome - reciprocal translocation of long arms of 9 & 22

Etiology of Leukemias - Causes:

1. Causal risk factors

a. Progression of chronic myelocytic leukemia

b. Polycythemia vera

c. Hodgkin disease

d. Chronic lymphocytic leukemia

e. Myelofibrosis,

f. Sideroblastic anemia

g. Ionizing radiation

2. Genetic predisposition [actual gene not known)

- Abnormal chromosomes

CLL [Chronic Lymphocytic Leukemia)

- Neoplastic transformation of lymphoid cells/B cells

- Both are well differentiated

- Etiology:

malignant TRANSFORMATION of predominantly B-cells