Clincial Correlates

Question 1

Anemia

Answer 1

Condition marked by either a low total RBC count or a decreased hematocrit/hemoglobin count

Question 2

Thalassemias

Answer 2

Genetic disorder related to the underproduction of hemoglobin via globin chain gene disorders(not dysfunctional though)

Can be caused via 2 reasons

• deletions of the entire gene
• substitutions or deletion of one or many nucleotide disorders

Are classified by a(+/-/0) and b(+/-/0) based on what chains are present and being produced

Two broad subtypes (alpha and beta)

Question 3

Hemoglobinopathies

Answer 3

Genetic disorders related to dysfunctional hemoglobin (not low numbers though)

Question 4

Polycythemia (erythrocytosis)

Answer 4

Increased RBC count caused by one of the following

• environmental factors
• pathological issues
• physiological (moving to high altitudes)

Causes increases in blood viscosity which increases Heart strain and impair circulation if severe

Question 5

Thrombocytopenia purpura

Answer 5

Circulating platelet function is impaired

• autoimmune or infections destroy circulating platelets leaving free platelet levels low
• presents with little red spots in patients*

Question 6

Hemophilia

Answer 6

Impaired clotting function (such as factor 7) usually via genetic disorder

Question 7

Eosinophilia

Answer 7

Increases in the number of circulating eosinophils usually associated with allergic reactions and parasitic infections

• treated via corticosteroids

Question 8

Anaphylaxis

Answer 8

Caused by a rapid systemic degranulation of mast cells and basophils resulting in extreme vasodilation of blood vessels

Results in sudden severe drop of blood pressure and can be lethal

Question 9

Lymphomas

Answer 9

General form of cancer due to excessive lymphocyte proliferation of lack of apoptosis (usually within a lymphoid organ/tissue)

• slow growing but are considered malignant. Given their easy of metastasis through the blood*

Question 10

Myeloproliferative disorders

Answer 10

Several abnormal proliferation of stem cells which progress slowly usuallyto leukemia’s

Question 11

Bandemia

Answer 11

Circulating high band cell count “shift to the left”. Usually signals a significant clinical finding such as bacterial infections and leukemia’s

Question 12

Ineffective megakaryopoiesis

Answer 12

Disruption in megakaryopoiesis leads to reduced production of platelets

different from thrombocytopenia purpura where the platelets are produced from normal levels of megakaryocytes, just the platelets are then destroyed

Question 13

Sickle cell anemia

Answer 13

Homozygous mutation that causes an amino acid substitution (usually resulting in a Val to glu which ultimately changes A -> T codon change) hemoglobin

• causes mature RBCs to appear sickle like and be inefficient at oxygen binding, as well as increase the chance of capillary blockage

Question 14

Carbon monoxide poisoning

Answer 14

Is dangerous because carbon dioxide competes directly with oxygen at the same site. Binding affinity for carbon monoxide is also much higher than oxygen, so it usually wins over oxygen and leads to suffocation, hypoxia and necrosis overtime.

Question 15

Neutrophil defects

Answer 15

Usually genetically caused issuers that lower the function of the neutrophils. Common examples are:

• decreasing adhesion to the wall of the venules
• absence of granules
• defective granules

Individuals affected present with persistent bacterial infections and higher than normal levels of macrophages.

Question 16

Type 1 hypersensitivity

Answer 16

Substances that cause an allergic production of specific IgE antibodies which then bind to receptors on mast cells and basophils

• subsequent exposures cause cross-linkage response and mass release of cytoplasmic granules

Symptoms:
Asthma, hives, rhinitis, conjunctivitis, allergic gastroenteritis

• can also result in anaphylactic shock*

Question 17

Glycoprotein 1b deficiency

Answer 17

Rare autosomal recessive disorder that affects this factor on platelet surface. This factor is required for binding collagen to platelets, so clotting rarely forms.

Question 18

Staph. Scalded Skin Syndrome (SSSS)

Answer 18

Usually presents in children under 5 years old and is caused by staph. Aureus

S. Aureus imitates 2 superantigens
- Epidermolytic toxins A and B

Symptoms:

• Bullae: sluffing off of skin and blisters
• Nikolsky’s sign: gently rub skin and the skin detaches and forms a blister

Question 19

IPEX syndrome

Answer 19

Immunedysregulation polyendocrinopathy Enteropathy X-linked syndrome

• caused by an X-linked defect in FoxP3 receptors
• cause autoimmunity to be disabled and T regulatory cells cant turn off T-cells so they attack self tissue

Symptoms:

• classic triad of: enteropathy, Endocrinopathy, Dermatitis
• Severe diarrhea
• Type 1 diabetes mellitus
• Overall organ damage

Diagnosis is done through flow cytometry showing double inactivation of CD4 cells and FoxP3

Question 20

Sickle cell disease

Answer 20

A qualitative hemoglobinopathy that results form a point mutation in the B-hemoglobin gene from glu - > lys

results in altered “sickle” like structure
- in the deoxygenated state, Hemoglobin becomes ridged due to the valine structure and causes sickle like appearance

Increases chances of clotting, microinfarcts, hypoxia and overall pain, especially in high altitudes
- the sickle structure poorly binds oxygen and is more prone to clotting in capillaries

• is autosomal recessive disorder (requires homozygous recessive to express trait)

Question 21

HbC disease

Answer 21

Amino acid substation in the B-chain glu -> lys

Symptoms:
- mild, chronic hemolytic anemia w/out infarction crises

Question 22

HbSC disease

Answer 22

Patients are double heterozygous (compound heterozygotes)
- both B-chains are abnormal

Symptoms:

• usually present with normal levels of hemoglobin (low end of normal)
• infarction crisis can be present but less likely than sickle cell (more than HbC though)

Question 23

Methemoglobinemias

Answer 23

Oxidation of heme iron turns hemoglobin into Methemoglobin (Fe3+ iron)
- this form of hemoglobin is UNABLE to bind oxygen properly

Can be acquired via interactions with chemicals and reactive oxygen species

Can be congenital
- NADH-cytochrome b5 reductase deficiency
( enzyme used to convert Fe3+ -> Fe2+

• a/b chain mutations that produce abnormal hemoglobin in the form of HbM
  (Type of hemoglobin that is resistant to reductase activity)

Symptoms
- chocolate cyanosis is the cardinal symptom
(blue skin/mucous membranes with brown blood)
- anxiety, headache and dyspnea
- coma/death if untreated

• this is hypothesized to cause the blue family disorder*

Question 24

Beta-Thalassemia

Answer 24

Synthesis of the B-globin chains are decreased or absent (-/0) whereas a-globin chains are normal levels (+)

Excess a-globin chains cannot form stable tetramers and the resulting precipitate increases premature death of reticulocytes

Can be B-minor or B-major(cooley anemia)
- B-minor = 1 of the 2 beta chain genes are defective. Make some but low levels of B-chain

• B-major/Cooley anemia = both beta chain genes are defective. Does not make any B-chains
• beta-chain genes are both located on chromosome 11*

Question 25

Alpha-thalassemia

Answer 25

Synthesis of Alpha chains is defective or absent (-/0) but beta chain production is normal (+)

4 types since there are 4 genes (all on chromosome 16)

• silent carrier: 1/4 genes defective and diseases is asymptomatic
• a-thalassemia trait: 2/4 genes defective and produce mild general anemia symptoms
• Hemoglobin H disease: 3/4 genes defective and produce mild-severe general anemia symptoms
• hemoglobin Bart diseaseL 4/4 genes are defective. Causes fetal death 100% of time (cant synthesis HbF)

Question 26

Thrombophillia (Hypercoagulability)

Answer 26

Disorders that increase risk of thrombosis occurring

Question 27

Tonsillitis

Answer 27

Chronic inflammation of the tonsils

• lymphoid nodules are always active and common in children

Question 28

Adenoids

Answer 28

Chronic inflammation and hyperplasia of the pharyngeal tonsils

Can obstruct the pharyngeotympanic tube and cause middle ear infections