Clincial Correlates Flashcards
Anemia
Condition marked by either a low total RBC count or a decreased hematocrit/hemoglobin count
Thalassemias
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)
Hemoglobinopathies
Genetic disorders related to dysfunctional hemoglobin (not low numbers though)
Polycythemia (erythrocytosis)
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
Thrombocytopenia purpura
Circulating platelet function is impaired
- autoimmune or infections destroy circulating platelets leaving free platelet levels low
- presents with little red spots in patients*
Hemophilia
Impaired clotting function (such as factor 7) usually via genetic disorder
Eosinophilia
Increases in the number of circulating eosinophils usually associated with allergic reactions and parasitic infections
- treated via corticosteroids
Anaphylaxis
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
Lymphomas
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*
Myeloproliferative disorders
Several abnormal proliferation of stem cells which progress slowly usuallyto leukemia’s
Bandemia
Circulating high band cell count “shift to the left”. Usually signals a significant clinical finding such as bacterial infections and leukemia’s
Ineffective megakaryopoiesis
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
Sickle cell anemia
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
Carbon monoxide poisoning
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.
Neutrophil defects
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.
Type 1 hypersensitivity
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*
Glycoprotein 1b deficiency
Rare autosomal recessive disorder that affects this factor on platelet surface. This factor is required for binding collagen to platelets, so clotting rarely forms.
Staph. Scalded Skin Syndrome (SSSS)
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
IPEX syndrome
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
Sickle cell disease
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)
HbC disease
Amino acid substation in the B-chain glu -> lys
Symptoms:
- mild, chronic hemolytic anemia w/out infarction crises
HbSC disease
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)
Methemoglobinemias
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*
Beta-Thalassemia
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*
Alpha-thalassemia
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)
Thrombophillia (Hypercoagulability)
Disorders that increase risk of thrombosis occurring
Tonsillitis
Chronic inflammation of the tonsils
- lymphoid nodules are always active and common in children
Adenoids
Chronic inflammation and hyperplasia of the pharyngeal tonsils
Can obstruct the pharyngeotympanic tube and cause middle ear infections
