Gastrointestinal and Hematologic Disorders Flashcards

Myelodysplastic Syndromes

• Definition: A group of hematopoietic disorders characterized by cellular dysplasia and pancytopenia (↓ RBC, WBC, and platelets).
• Synonyms: Dysmyelopoietic syndrome, hematopoietic dysplasia, pre-leukemia, refractory anemia.
• Classifications: Refractory anemia, chronic myelomonocytic leukemia, refractory anemia with excess blasts in transformation.

Epidemiology

• Predominant Age: Elderly, >65 years.
• Children: Uncommon.
• Progression: May progress to acute myeloid leukemia (AML).
• Predominant Sex: Male = Female.
• Incidence: 1-2/100,000 per year.

Risk Factors

• Exposure to benzene and gasoline.
• Smoking.
• Treatment with alkylating agents or radiotherapy.
• Genetic factors: G6PD mutation, RAS oncogene mutation.
• Clonal neoplasms by cytogenetic abnormalities.
• Unknown etiology.

Pathophysiology

• Clonal hematopoiesis leading to expansion of abnormal clones and apoptosis.
• Genetic mutations leading to increased apoptosis in the early stages.
• Ineffective hematopoiesis causing anemia, neutropenia, and thrombocytopenia.

Signs & Symptoms

• Anemia: Fatigue, pale skin, shortness of breath, lightheadedness, angina.
• Leukopenia: Fever, increased risk of infection.
• Thrombocytopenia: Easy bruising, petechiae, epistaxis, purpura.
• **Skin infiltrates.
• Splenomegaly: Uncommon, but may occur in chronic myelomonocytic leukemia (CMML).

Diagnosis

• Cytogenetic tests for clonal chromosomal abnormalities.
• Rule out other causes: nutritional deficiencies, toxic exposures, autoimmune disorders.
• Granulocyte function test.
• Platelet function test.
• Marrow colony assays.
• Immunophenotyping.

Laboratory Findings

• Increased MCV (macrocytic anemia).
• Reticulocyte count (may be elevated or normal).
• Bone marrow failure.
• Anemia: Macrocytic (MCV > 100), poikilocytosis, anisocytosis, reticulocytosis.
• Granulocytopenia: Hypogranular or agranular neutrophils.
• Thrombocytopenia: Giant platelets or hypogranular platelets.
• HbF (fetal hemoglobin): Should be ruled out as a cause; Thalassemia; HbF fetus stage.
• Coombs test: To rule out hemolytic anemia.
• Imaging: Liver/spleen scan for splenomegaly or lymphadenopathy.
• Bone marrow aspiration, biopsy: Hypercellular with increased blasts.
• Peripheral blood smear.

Differential Diagnosis

• Myeloproliferative disorders (no cytopenia).
• AML or erythroleukemia (acute).
• Chronic myeloproliferative disorders (adequate maturation).
• Polycythemia Vera (too much blood production, Hb 17-18).
• Myeloid metaplasia with myelofibrosis.
• Malignant lymphoma.
• Metastatic carcinoma.

Treatment

• Immunizations: Pneumococcal pneumonia, influenza, Hep B.
• RBC transfusions.
• Platelet transfusions.
• Early antibiotic use.
• Diet: Avoid alcohol and iron intake.
• Medications:
  • 1st line: Azacytidine, Decitabine, Lenalidomide.
  • Chemotherapy.
  • Bone marrow transplant.
  • 2nd line: Low dose cytarabine, interferon, cyclosporine, granulocyte colony-stimulating factor.

Prognosis

• Refractory anemia (survival: 5 years or longer).
• Others: 1 year (death due to AML or infection/bleeding).

Complications

• Infection.
• Bleeding.
• Complications of anemia and transfusion.
• Citrate toxicity -> Urolithiasis (from citrate in blood bags).

Acute Myeloid Leukemia (AML)

• Synonyms: Acute myelogenous leukemia, acute granulocytic leukemia.
• Definition: Cancer of the blood and bone marrow affecting myeloid cells (↓ RBC, WBC, platelets) with rapid growth of abnormal WBCs.

Epidemiology

• Adults > 45 years.
• 1% of all cancer types.

Risk Factors

• Age (more common in older adults).
• Sex: Male > Female.
• Smoking (leads to lung cancer).
• Exposure to chemicals: Benzene, oil refinery, shoe manufacturing, gasoline.
• Exposure to formaldehyde.
• Chemotherapy drugs: Alkylating drugs (Cyclophosphamide, Procarbazine, Busulfan).
• High dose radiation exposure.
• MDS.
• Genetic: Fanconi anemia, Bloom syndrome, Neurofibromatosis type I.
• Family history.

Etiology

• Abnormality of chromosome aging.
• Genetic mutations.
• Changes in DNA affecting control functions.
• Decrease in tumor suppressor genes.

Diagnosis

• Screening tests for early detection are not helpful in AML.
• Blasts in AML.

Signs & Symptoms

• Non-specific: Weight loss, fatigue, fever, night sweats, loss of appetite.
• Leukopenia: Fever, infection.
• Thrombocytopenia: Bruises, excess bleeding, nosebleed, bleed gums, heavy periods.
• Confusion.
• Splenomegaly.
• Hepatomegaly.
• Bone marrow infiltration.
• Enlarged lymph nodes.
• Swelling, pain, bleeding gums.

Subtypes

• Goal: for easier treatment
• M0-M5: Immature forms of WBC- monocyte
• M6: Very immature forms of RBC- erythroblast
• M7: Immature forms of platelet making.

Prognosis

• Depends on factors, subtypes.

Treatment

• Refers to Oncology department.
• Chemotherapy.
• Radiotherapy.

Differential Diagnosis MDS vs AML

• Blasts <20% vs Blasts ≥20%.

Chronic Myeloid Leukemia (CML)

• Definition: Cancer of WBCs characterized by increased unregulated growth of myeloid cells in bone marrow and accumulation in blood.
• Chronic > 3 months without proper treatment.
• Differentiate of MDS, AML, CML.

Epidemiology

• Male > Female.
• Age: Any age, mostly 60 years.
• Adults (mainly), children (rarely).

Risk Factors

• Expose skin to strong sunlight.
• Smoking.
• High dose radiation exposure (atomic bomb or nuclear).
• Aging.
• Sex: Male > female.
• G6PD deficiency.

Etiology

• Chromosome 9 and 22 swapped (Philadelphia chromosome).
• Defected chromosome (oncogene): BCR-ABL gene.
• Produce protein cause CML grow & divide out of control.

Signs & Symptoms

• Weakness.
• Fatigue.
• Night sweats.
• Weight loss.
• Fever.
• Risk of infection.
• Bone pain, joint pain (caused by leukemia spreading from marrow cavity to bone or joint).

Diagnosis

• Screening CBC: abnormity of RBC, WBC, platelets.
• Tumor marker (should be next if CBC level is normal/abnormal).
• Lab test: Increased WBC, immature myeloblasts, increased platelets.
• Bone marrow biopsy: Hypercellularity with myeloid hyperplasia.
• Philadelphia chromosome presence.

Phases of CML

• Chronic phase: Blasts <10%; more responsive to tyrosine kinase inhibitors.
• Accelerated phase: Basophilia, blasts 15%; not respond well to treatment.
• Blast phase: Large cluster of blast in bone marrow, Blasts ≥20%; like AML symptoms, refractory.

Prognosis

• Depends on CML phases.

Liver Cirrhosis

• Definition: Chronic liver disease leading to inflammation, necrosis, fibrosis, and stellate activation - end result liver failure or cancer
• Definition Chronic liver disease (alcohol abuse)Chronic Liver disease (non-alcohol +obesity) -> liver steatosis (fatty liver disease) -> fat + liver secrete enzyme irritate hepatocyte -> prolong -> liver steatosis.

Epidemiology

• Predominant age: 40-50 /peak incidence
• Predominant sex: Male
• Alcohol abuse -15th cause of death at 45-54 yrs
• 12 cause of death in US adults

Genetics:

• hemochromatosis
• wilson disease
• a1-Antitrypsin deficiency in adults

Etiology & Pathophysiology

• Toxins -> hepatocyte injury -> secrete paracine factor to become -> activate & change stellate -> transforming growth factor-B-1
• Virus -> stellated -> lose vit. A & start secrete TGF-B1
• Produce collagen - extracellular matrix -> fibrosis & scaring compress central vein & sinusoid but normally healthy liver state stellated function wound healing on liver injury cirrhosisbile stasis (gallstone, duct obstruct bile reflux into liver-
• Metabolic disorder (PTG + poor liver inflammation -> liver steatosis)
• Autoimmune disease

Risk Factors

• Alcohol abuse
• History of viral hepatitis
• Family history of primary liver cancer
• Signs & Symptoms
• Asymptomatic early stage (liver compensate I still get - work done)
• Non-specific : weight loss , weakness, fatigue, anorexia
• Late stage (liver decompensate) -> extensive fibrosis (malfunction

Clinical Manifestations of decompensated liver state

• Skin changes spider angiomata - superficial vein
• Xanthoma(cholesterolmotiveheimer liver malfunction
• hyperpigmentation
• jaundice
• Caput medusa Overflow of fluid in belly (joy belly & umbilical cord vory/o)
• Leg edema
• Hepatomegaly, splenomegaly , cirrhotic liver