Diseases Flashcards
thalassemia
Thalassemia is an inherited blood disorder characterized by less hemoglobin and fewer red blood cells in the body than normal. The low hemoglobin and fewer red blood cells of thalassemia may cause anemia. It is a globin chain defect.
- microcytic anemia
- elevated RBC
- no significant anisocytosis
- alpha or beta chains
Hereditary Spherocytosis (HS)
- autosomal dominant disorder
- microvesiculation + membrane loss = spherical RBCs
- defects in ankyrin gene most common - defects of Band 3 and alpha spectrin rare
- decreased flexibility makes it hard for the RBC to pass through small channels; getting caught in splenic sinusoids leads to phagocytosis and destruction by splenic macrophages
- anemia with marked reticulocytosis
- jaundice
- splenomegaly
- variable anemia from present at birth to asymptomatic
PIGA gene anemia
*Increase complement-mediated intravascular RBC lysis secondary to acquired
somatic X-chromosome mutation in PIGA gene in a hematopoietic stem cell
(affects RBC, neutrophils, monocytes, and platelets).
*Clinical presentation: florid intravascular hemolysis (hemoglobinuria), thrombosis (40%), smooth muscle dystonia, abdominal pain. All ages and ethnic groups are affected, though in children is rare. Associated with aplastic anemia.
*Peripheral blood findings: Triad: Direct Coombs (DAT) negative
hemolytic anemia, pancytopenia and venous thrombosis.
Normochromic normocytic anemia, increased polychromasia (high
reticulocyte count).
* Diagnosis: Complement-mediated lysis of GPI-AP deficient cells.
Often more than 50% of the polymorphonuclear cells are GPI-AP
deficient (lack of CD55 and or CD59 by flow cytometry). Neutrophils
may have shorter telomeres.
*Treatment: eculizumab – inhibits terminal complement formation
Sickle Cell Anemia
*point mutation leading to a single amino acid substitution of
valine for glutamine in β globin gene.
*Under oxidative stress, HbSn polymerizes and crystallizes leading to characteristic sickle shape of the
RBCs. HbS polymerization is initially reversible with re-oxygenation, but with
repeated cycles of sickling, the damage becomes irreversible. This leads to
secondary membrane damage, inflexibility, hemolysis and vaso-occlusive
disease.
*Sickle cell trait: 8% of African Americans carry an HbS allele. Rarely causes
sickling or anemia, except under severe conditions. Sickle cell trait confers
resistance to malaria.
*Sickle cell disease (homozygous HbS): Low O2 saturation, high altitude,
acidosis precipitate sickling leading to anemia and vaso-occlusive disease.
Newborns have high concentration of HbF (2α 2γ chains) and low HbS, so
sickling is not seen until fetal hemoglobin levels decline. Intracellular factors
that affect the MCHC will affect the severity of the disease (e.g. dehydration
makes it worse; decreased globin production as is seen in α-thalassemia,
makes it better). Acidosis (often seen with hypoxia) will also increase the
tendency to sickle.
*Peripheral blood findings: RBC anisocytosis, poikilocytosis, sickled cells,
reticulocytes; extramedullary hematopoiesis
Complications of sickle cell disease:
• Chronic hemolytic anemia
• Painful crisis = vaso-occlusive crisis in bones (hand-foot syndrome or leg
ulcers), lungs (acute chest syndrome), penis (priapism), brain (seizure or
stroke), liver or spleen (infarct)
• Aplastic crisis = sudden stop of marrow RBC production (Parvovirus B19)
• Sequestration crisis = sudden accumulation of RBCs in the spleen due to
sludging
• Autosplenectomy: increase risk of infections (loss of splenic function;
defective complement opsonization). RBC with Howell-Jolly bodies
• Microinfarcts expanding to gross infarcts, especially in solid organs (liver,
brain, kidneys), but also in the lungs (cor pulmonale);
• Bone marrow expansion with thinning of cortical bone (“crew cut” or “hairon-end” appearance of skull x-rays)
*Diagnosis: clinical findings, peripheral smear with sickle cells; hemoglobin
electrophoresis; prenatal DNA testing for affected fetus
Duchenne MD
- The disorder is X-linked recessive.
- About two thirds of cases are inherited from a person’s mother, while one third of cases are due to a new mutation.[2] It is caused by a mutation in the gene for the protein dystrophin. Dystrophin is important to maintain the muscle fiber’s cell membrane. Genetic testing can often make the diagnosis at birth. Those affected also have a high level of creatine kinase in their blood.
- Although there is no known cure, physical therapy, braces, and corrective surgery may help with some symptoms.[1] Assisted ventilation may be required in those with weakness of breathing muscles.[2] Medications used include steroids to slow muscle degeneration, anticonvulsants to control seizures and some muscle activity, and immunosuppressants to delay damage to dying muscle cells.
- DMD affects about one in 5,000 males at birth. It is the most common type of muscular dystrophy. The average life expectancy is 26;however, with excellent care, some may live into their 30s or 40s.Gene therapy, as a treatment, is in the early stages of study in humans.
- Awkward manner of walking, stepping, or running – (patients tend to walk on their forefeet, because of an increased calf muscle tone. Also, toe walking is a compensatory adaptation to knee extensor weakness.)
- Frequent falls
- Fatigue
- Difficulty with motor skills (running, hopping, jumping)
- Lumbar hyperlordosis, possibly leading to shortening of the hip-flexor muscles. This has an effect on overall posture and a manner of walking, stepping, or running.
- Muscle contractures of Achilles tendon and hamstrings impair functionality because the muscle fibers shorten and fibrose in connective tissue
- Progressive difficulty walking
- Muscle fiber deformities
- Pseudohypertrophy (enlarging) of tongue and calf muscles. The muscle tissue is eventually replaced by fat and connective tissue, hence the term pseudohypertrophy.
- Higher risk of neurobehavioral disorders (e.g., ADHD), learning disorders (dyslexia), and non-progressive weaknesses in specific cognitive skills (in particular short-term verbal memory), which are believed to be the result of absent or dysfunctional dystrophin in the brain.
- Eventual loss of ability to walk (usually by the age of 12)
- Skeletal deformities (including scoliosis in some cases)
- Trouble getting up from lying or sitting position
AML (acute myeloid lymphoma)
*mutations in the TCEB1 gene
VHL (Von Hippel-Landau syndrome)
- associated with non-malignant blood vessel tumors in critical organ systems including the brain, spinal cord, kidney and retinal
- the protein pVHL encoded by the Von Hippel-Landau gene VHL interacts with TCEB1 and mediates the action for transcription factor HIF-alpha.
Plummer Vinson Syndrome
- microcytic/hypochromic anemia
- glossitis
- esophageal webs
- iron deficiency anemia
Autoimmmune Hemolytic Anemia
- destruction of RBCs by complement and phagocytes
* Type II Hypersensitivity
Goodpasture’s Syndrome
- antigen: collagen type IV
- glomerulonephritis
- pulmonary hemorrhage
- Type II Hypersensitivity
Grave’s Disease
- antigen: thyroid stimulating hormone receptor on thyroid follicular cells
- hyperthyroidism
- Type II Hypersensitivity
Systemic Lupus Erythematosus
- antigen: DNA, histones, ribosomes, snRNP, scRNP
- glomerulonephritis, vasculitis, arthritis
- helper T cells, Type II Hypersensitivity, Type III Hypersensitivity
Type I Diabetes
- antigen: pancreatic beta cells
- Type IV Hypersensitivity
- inability to regulate blood glucose
Multiple Sclerosis
- antigen: myelin basic protein, proteolipid protein
- Type IV Hypersensitivity
- visual impairment, ataxia, motor and sensory impairment
Crohn’s Disease
- antigen: microbiota, intestinal cells???
- transmural inflammation of the gut
- diarrhea, abdominal pain, intestinal obstruction
- Type IV Hypersensitivity
Hashimoto’s Thyroiditis
- thyroid antigens (thyroglobulin, thyroid peroxidase)
* fatigue, cold intolerance due to progressive destruction of thyroid tissue and decreased thyroid hormone
Rheumatoid Arthritis
- antigen:unknown synovial joint antigen
- joint inflammation and destruction
- Type IV Hypersensitivity
Sjogren Syndrome
- antigen:unknown antigens in salivary and lacrimal glands
* dry eyes and dry mouth
Systemic Sclerosis
- antigen: topoisomerase I, centromere antigens, others
- thickened skin (starting distally, progressing), fatigue, arthralgias, myalgia
- Type IV Hypersensitivity
