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Advanced Patho Exam 1
Hyperplasia - an increase in a # of cells in an organ or tissue resulting from an increased rate of cellular division. Occurs in response to an injury that results when the growth factors, which stimulate remaining cells (after cell loss or injury) to synthesize new cell components, and ultimately divide. Hypertrophy - the increase in the size of cells that consequently increases the size of the affected organ. Heart and Kidneys are particularly responsive to enlargement. Physiologic-caused by increased demand, stimulation by hormones and growth factors. Pathologic- results from chronic hemodynamic overload, HTN or valve dysfunction. Atrophy - decrease or shrinkage in cell size. If occurs in significant #, entire organ or tissue shrinks and becomes atrophic. Can affect any organ, most common in skeletal muscles, secondary sex hormones, heart and brain. Dysplasia - Refers to abnormal changes in the size, shape and organization of mature cells. Not considered a true adaptive processes, and usually related to hyperplasia, often referred to as atypical hyperplasia. Dysplastic changes usually found in epithelia. Is not cancer and may not lead to cancer, can be reversed. When invades basement membrane, considered preinvasive neoplasm and is known as carcinoma in situ. Metaplasia - Reversible replacement of 1 cell type (epithelial or mesenchymal) with another type of cell, sometimes less differentiated. Found in association with tissue damage, repair or regeneration. New cell may be better suited, ie GI Reflux, epithelial cell replaced with glandular which does better in that environment. NOT usually beneficial, long term smokers normal ciliated epithelial cells replaced with striated squamous cells that do not secrete mucous or have cilia. Role of Vasopressin in Fluid Retention - action is to increase permeability of distal renal tubular cells to water, increasing water reabsorption and promoting the restoration of plasma volume and blood pressure. (Body keeps volume) Role of Aldosterone in Fluid Retention - promotes sodium and water reabsorption by the proximal tubules in kidneys, thus conserving sodium, blood volume, and blood pressure. (Body keeps volume) Role of Atrial Natriuretic Peptide in Fluid Retention - ANP increases sodium and water excretion by the kidneys, which lowers blood volume and blood pressure. (Body loses volume) Hypercalcemia - high calcium greater than 10.
caused by-hyperparathyroidism, bone metastases with calcium resorption from breast, prostate, renal & cervical cancer, sarcoidosis, excess VitD, tumors containing PTH and calcium containing antacids. Clinical-fatigue, weakness, lethargy, anorexia, nausea, constipation, impaired renal function, kidney stones, dysrhythmias, bradycardia, cardiac arrest, bone pain, osteoporosis, fractures. Hypocalcemia - low calcium-less than 8. caused by-inadequate intestinal absorption, deposition of ionized calcium into bone or soft tissue or decrease in PTH or VitD, nutritional with inadequate sources of dairy, leafy green vegetables. Clinical-increased neuromuscular excitability, tingling, muscle spasms-hands, feet, face-intestinal cramping, hyperactive bowel sounds, osteoporosis and fractures, severe cases=convulsions and tetany, prolong QT interval, cardiac arrest. TX-severe, ER IV 10% calcium gluconate, oral calcium, decreasing phosphate intake. Hyperchloremia - greater than 105 caused by-excess sodium or a deficit of bicarb. clinical-looks like hypernatremia TX-correct underlying cause Hypocloremia - less than 97 caused by-hyponatremia, or elevated bicarb (metabolic alkalosis) use of diuretics, vomiting clinical-looks like hyponatremia TX-correct underlying cause Hypernatremia - high sodium greater than 145 caused by-excess of sodium or loss of water in ECF, excessive sweating, fever, burns, respiratory infection, diabetes insipidus, osmotic diuresis, osmotic diarrhea, seizures clinical-brain dehydration, lethargy, weakness, twitches, irritability, coma, death, hemorrhages Hyponatremia - Low Sodium less than 135 caused by-loss of sodium, gain of water, compensation for decreased blood flow, diuretics, renal disease, SIADH Clinical-hypo osmolality, EC osmolality decrease, cells swell, cerebral overhydration, edema, nausea, headache, malaise, alterations in action potentials TX-increase sodium intake, raising Na levels, treat cause, give Na especially if caused by true volume depletion, diuretics, adrenal insufficiency) would restrict water if caused by tooLow Sodium less than 135 caused by-loss of sodium, gain of water, compensation for decreased blood flow, diuretics, renal disease, SIADH Clinical-hypo osmolality, EC osmolality decrease, cells swell, cerebral overhydration, edema, nausea, headache, malaise, alterations in action potentials TX-increase sodium intake, raising Na levels, treat cause, give Na especially if caused by true volume depletion, diuretics, adrenal insufficiency) would restrict water if caused by too much water (SIADH, renal failure, polygenic/polydipsia
low phosphate less than 2. caused by-intestinal malabsorption r/t vitamin D deficiency, use of magnesium and aluminum containing antacids, long-term alcohol abuse, and malabsorption syndromes, respiratory alkalosis, increased renal excretion of phosphate associated with hyperparathyroid. clinical-conditions related to reduces capacity for O2 transport by RBC and disturbed energy metabolism, leukocyte and platelet dysfunction, deranged nerve and muscle function, in severe cases, irritability, confusion, numbness, coma, convulsions, possible respiratory failure r/t muscle weakness, cardiomyopathies, bone resorption leading to rickets or osteomalacia. TX-correcting underlying cause Autosomal Dominant - -rare=normal parent with affected heterozygous parent -one copy causes phenotype EX-Achondroplasia (dwarfism) -no skipping generations, one parent must have it. -females and males equally as likely to transmit -1/2 of the children from heterozygous individuals will develop Achodroplasia Autosomal Recessive - -need two copies to cause phenotype -carriers do not display phenotype but may have subtle differences because they are creating less of the protein than normal -both parents have to be carriers. -males and females are affected equally -EX Tay sachs disease X-Linked Dominant - -very rare -need only have one copy to have disorder -females may experience less severe symptoms -95% of time, spontaneous mutations because typically not compatible w life. -mother is affected and unaffected father, mother has 50/50 of passing on chromosomes to each child regardless of gender -father is affected, he will only passing on his X chromosomes to his daughters. -EX-RETT Syndrome X Linked Recessive - -Need two copies of affected X in order to have the disease, only female carriers -can inherit the mutation from their father but have a healthy X to offset the affected X -men cant be just carries, only 1 X so have mutation. -mostly boys affected because girls have healthy X to produce enough healthy protein at that location. -EX color blindness, hemophilia Turner Syndrome - Transmission-(females) one X is partially or completely absent. 3 scenarios (at random):
- entire X is missing, 45 chromosomes (meiosis)
- Mosaicism, some cells with 45 chromosomes and some cells with 46 (mitosis)
- part of X chromosome is missing, (meiosis & mitosis)
Physical Manifestations-short stature, cardiovascular defects, horseshoe kidneys, lymphatic abnormalities, skeletal abnormalities, increased risk for DM2, hypothyroidism, neck webbing, blue discoloration of lower limbs, widely spaced nipples, broad chest, arms that turn outward, streak ovaries, amenorrhea Klinefelter Syndrome - Transmission-Male inherits 1 extra X (XXY) Physical Manifestations-low test, less or small sex organs, hypogonadism, sterile, tall, long legs, short torso, broad hips, gynecomastia, less muscle mass, weaker bones, less facial and body hair, lower energy levels, possible gender identity crisis Cri Du Chat Syndromw - Transmission-deletion of part of short arm of Chromosome 5, usually not inherited Physical Manifestations- unique cry, low birth wt, severe intellectual disability, microcephaly, heart defects, facial features Trisomies - 3 copies of chromosomes, 13, 18, 21 13-Patau Syndrome -Most cases full trisomy, few cases from Mosaicism (building blocks of chromosomes are rearranged) -multiple anomalies of CNS, face, heart & extremities 18-Edward Syndrome -95% extra 18, 5% translocation in which building blocks of 1 chromosome are inserted in another. -IUGR, multiple anomalies of CNS, face, heart & extremities*usually do not survive past yr 21-Down syndrome -can be a complete, translocation or mosaicism -increased risk of medical problems, varying degrees of mental development, round face, upturned eyes, short & stalky build Huntington's Disease - Condition in which nerve cells breakdown over time. -Autosomal dominant -(symptoms appear age 40 or over, progressive dementia, increasingly uncontrollable movements of limbs Prader-Willi Syndrome - Deletion of 4 million base pairs of long arm of chromosome 15 -inherited from father -short stature, hypotonia, small hands/feet, obesity, mild to mod intellectual disability, hypogonadism Innate Immunity - -Present at birth -non-specific -limited # of germ line encoded receptors -begins within minutes to hours after birth -monocytes and macrophages, NK cells, dendritic cells Adaptive Immunity - -self/non-self recognition
-requires previous sensitization -mast cells release (histamine) -immediate, develops with in minutes of exposure to a sensitized individual or animal to antigen -vascular permeability, vasodilation, bronchial and visceral smooth muscle contraction, local inflammation -EX seasonal allergies Type II Hypersensitivity (cytotoxic) - IgE, IgM -antibody mediated -immediate -macrophages in tissue -antibodies bind to normal or altered antigens on cell surface resulting in opsonization, phagocytosis, inflammation then dysfunction. -promotes cell lysis and phagocytosis -EX autoimmune thrombocytopenic purpura. hemolytic anemia, transfusion reactions Type III Hypersensitivity - -IgG, IgM -immune complex mediated rxn -immediate -neutrophils -can be systemic or localized -uses circulating antigen-antibody complexes by which the antibody binds to soluble antigen and are deposited in blood vessel walls, can cause joint, kidney problems -EX (not organ specific) systemic lupus, fever, proteinuria, arthritis Type IV Hypersensitivity - -NO Immunoglobulins, only hypersensitivity involves T-cells -cell mediated rxn -delayed -lymphocytes, macrophages -sensitized by CD4 & 8, T-cells attack and destroy cellular targets directly and cause destruction of tissue. Seen frequently in autoimmune disorders but also post-viral infections -48-72 hours for clinical manifestations -EX Guillain Barre, Type 1 DM, rheumatoid Pathophysiology of Systemic Lupus Erythematosus (SLE) - -autoimmune -chronic, multi-system inflammatory disease -1 of the most common, complex and serious AI -occurs at multiple sites of connective tissue: arthralgias, arthritis, vasculitis, reash, renal disease, hematologic abnormalities (anemia) cardiovascular disease. -Females: alopecia, photosensitivity, oral ulcers, malar rash, lupus, anticoagulant, arthritis, serositis w/pleurisy/pleuritis (causes pleuritic chest pain) Males: thrombocytopenia, anti dnDNA, renal involvement -develops slowly (10 years) reoccurrence, hard to dx -lab dx: positive ANA test
-no cure, fatalities due to cardiovascular disease, organ failure, infection -goal: prevent further damage by suppressing autoimmune response. -TX: NSAIDS, low dose corticosteroids, high dose pred, hydroxychloroquine, severe cases- immunosuppressant drugs: methotrexate, azathioprine, cyclophosphamide, IVIG TX- -UV Light may make worse -Type III Hypersensitivity Pathogenesis of HIV - Pathogenesis: 2 variants-HIV-1 & HIV-2 (less virulent) Member of retrovirus fam, carries genetic info in 2 identical copies of single-stranded RNA
- enters body
- selective tropism ( the turning of all or part of an organism in a particular direction in response to an external stimulus) for cd4 cells 3.binding of HIV to cd4 + t cell through GP 120
- internalization (the process of adopting)
- viral genome undergoes reverse transcription
- production of cdna enters T cells
- active cd4 + t cell and inactive cd4 + t-cell
- budding of viral particles leads to productive infection leads to cytopathic phase
- divided into quantitative destruction and qualitative destruction
- impaired ability to provide an immune response Progression of HIV - Phase I: Asymptomatic P2: CD4+ t cells reduce steadily, only few infected cells release virus, few serious disease symptoms (fever, persistent infections, oral leukoplakia) P3: AIDs develops, Cd4+ is count below 200 cells/ 200 ul; indicator conditions Clinical Manifestations of Each Stage of HIV - Stage 0-acute viral syndrome, fever, fatigue, headache, lymphadenopathy, pharyngitis, myalgia, arhtralgia, skin rash may be extensive, without knowledge of exposure, pt may believe influenza infection present. Stage 1-CD4 T cell counts still normal, by 180 days, initial burst of viremia and acute viral syndrome will have resolved. Asymptomatic, infectious HIV present, destruction of CD4 cells have begun. Stage 2-diminished # of CD4 T cells Stage 3-defined as AIDS, CD4 T cells < 750 or AIDS r/t opportunistic infections regardless of CD4 T cell count Opportunistic Infections of Stage 3 HIV/AIDS - -protozoal & helminthic infections: cryptosporidosis, isosporiasis, toxoplasmosis of brain -fungal: candidiasis, coccidiodomycosis, cryptococcidosis, histoplasmosis, pneumocytis -bacterial: mycobacterium avium, mycobacterium tuberculosis, mycobacterium unspecified, recurrent pneumonia, salmonella septicemia -viral: cytomegalovirus, cytomegalovirus retinitis, herpes simplex-chronic ulcers, progressive multifocal leukoencephalopathy -Neoplasms: cervical-invasive, kaposi sarcoma, Burkitt, immunoblastic, primary of the brain lymphoma -HIV associated disorders: encephalopathy, wasting syndrome
-Clinical Manifestations - develops slowly (over 20-30 years), early symptoms non specific - infections, mood swings, GI, cardiac and kidney ailments. Classic symptoms of anemia (hgb less than
- weakness fatigue, parentheses of the hands and feet, abdominal pains, weight loss, sore tongue that is smooth and beefy red (secondary to atrophic glossitis, "yellow" lemon skin (in more severe), pallor. Neurological manifestations result from nerve demyelination - ataxia, loss of position and vibration sense, spascity, neurocognitive disorders (neuro disorders are NOT reversible with treatment) Folate Deficiency - -Occurs due to low level of folic acid in the body -Folate is essential to RNA and DNA synthesis -Folate comes from (vitamin B9) comes from leafy greens, citrus fruits and fortified grains and cereals -Pathophysiology - impaired DNA synthesis secondary to folate deficiency results in megaloblastic cells with clumped nuclear chromatin. Also anemia may result from apoptosis of erythroblasts in late stages of erythropoiesis. Folate deficiency in pregnant women is associated with neural tube defects of the fetus. -Clinical manifestations - severe cheilosis (scales and fissures of the lips and corners of the mouth), stomatitis (inflammation of the mouth), painful ulcerations of the buccal mucosa and tongue, burning mouth syndrome, dysphagia, flatulence, watery diarrhea. Does NOT cause neurological defects like B12 deficiency -Labs: measurement of serum folate levels, Those at risk - alcoholics (because alcohol interferes with folate stored in the liver) and malnourished individuals Iron Deficiency Anemia - -Most common type of anemia develops slowly -Causes - dietary deficiencies, impaired absorption, increased requirement, chronic blood loss -Pathophysiology - hypochromic microcytic anemia. Occurs when iron stores are depleted Dietary deficiencies or excessive blood loss - deplete iron stores and reduce hgb synthesis metabolic/malabsorption iron deficiencies - insufficient iron delivery to bone marrow or impaired iron use within the marrow. Iron levels may be sufficient but impaired delivery to bone marrow. -Clinical manifestations - symptoms begin gradually and symptoms don't appear until hgb around 7- g/dl. Early symptoms are nonspecific - fatigue, weakness, shortness of breath, pale earlobes, palms and conjunctiva. As disease progresses - fingernails become brittle, thin and coarsely ridged and spoon shaped or concave (koilonychia) as a result of impaired circulation. Also burning mouth syndrome like folate deficiency. Other symptoms - dryness and soreness in epithelial at the corner of mouth (angular stomatitis), dysphagia, hyposalivation. Epithelial lesions have the potential to become cancerous. Also can exhibit gastritis, neuromuscular changes, irritability, headache, numbness/tingling and vasomotor disturbances. Children can have cognitive impairment that may be irreversible -Labs - decreased levels of hgb and hematocrit, low serum iron, ferritin, and transferrin saturation levels. Anemia Of Chronic Disease - -Decreased erythropoiesis and impaired iron utilization in individuals with chronic systemic disease or inflammation (infections, cancers and chronic inflammatory or autoimmune diseases). Usually secondary to chronic disease. -Pathophysiology- 1. Decreased erythropoietin life span. 2. Suppressed production of erythropoietin.3. Ineffective bone marrow erythroid progenitor response to erythropoietin. 4. Altered iron metabolism and iron sequestration in macrophages.
-Clinical manifestations- mild to moderate range with few additional complications. If hgb drops significantly then clinical manifestations of IDA occur. See above. -Labs - Most significant finding is very high total body storage of iron but inadequate iron is released from bone marrow for erythropoiesis. First indication of ACD is failure to respond to iron replacement therapy. Polycythemia Vera - -Pathophysiology: chronic neoplastic nonmalignant myeloproliferative disorder→ over production of RBC. increase in WBC, platelets, and splenomegaly. Abnormal regulation of the multipotent hematopoietic progenitor cell Acquired point mutation in the Janus Kinase 2 gene. (JAK2) on chromosome 9. These red blood cell precursors reveal sensitivity to IL-3, GCF, or insulin-like factor. -Clinical manifestations: Enlarged spleen, abdominal discomfort, pain. Increased viscosity→ hypercoagulability→formation of venous and arterial thrombosis. Thrombi of major tissue/organs may lead to organ injury (ischemia) and death (infarction). Extreme thrombocythemia (>1,500,000) may increase the risk for bleeding, rather than thrombosis. Plethora: ruddy, red color of the face, hands, feet, ears, and mucous membranes Engorgement of the retinal and cerebral veins Headache, drowsiness, delirium, mania, psychotic depression, chorea, visual disturbances Death from cerebral thrombosis Elevated blood flow→ HTN, angina Raynaud phenomenon, thromboangiitis obliterans Splenomegaly, hepatomegaly, portal hypertension Intense painful itching when exposed to heat or showering -Labs: Increase RBC (14 to 28) HCT 60% or higher Bone marrow exam JAK 2 mutation Increase fibrosis PLT Basophils PT Thrombocytopenia - -Pathophysiology: Bone marrow is not making enough platelets. Platelets are destroyed or accumulate within an enlarged spleen. May be the results of chemotherapy or malignancy in the bone marrow (leukemia). -Clinical manifestations: Spontaneous bruise/bleeding, petechiae, purpura, mucosal bleeding, gingival bleeding. -Labs: PLT <100,000. PLT less than 15,000 may result in spontaneous bleeding. Less than 10,000 may be fatal. Disseminated Intravascular Coagulation (DIC) - -Pathophysiology: Complex, acquired disorder. Causes: Sepsis, cancer or acute leukemia, trauma, blood transfusion. Consumption of coagulation factors and platelets. Widespread and ongoing clotting activation.
Infectious Mononucleosis (mono) - Etiology *Acute, benign & self-limiting lymphoproliferative condition characterized by acute infection of B Lymphocytes *Most commonly comes from EBV (Epstein Barr Virus)85% *Part of Herpes Virus Group *Transmission primarily via saliva. -Clinical Manifestations *incubation 4-8wks *3-5 days of: fever, malaise, pharyngitis-usually accompanied by whiteis or grayish-green exudate, painful, lymphadenopathy. *severe cases can result in enlargement of spleen or liver. *rarely requires medical intervention beyond symptom control. Acute Myeloid Luekemia - Pathophysiology-aggressive, fast growing leukemia with an excessive number of myeloblasts (immature WBC that are not lymphoblasts, found in bone marrow and blood. *cause unknown but increased incidence with other hereditary abnormalities such Down's Syndrome, Trisomy 13, etc in children. *increased risk in adults linked to cigarette smoke, benzene, ionizing radiation. *Genetic aberrations in AML altar genes encoding transcription factors needed for normal myeloid differentiation; consequently, differentiation becomes arrested. -Clinical Manifestations: *anemia *bleeding (ecchymosis, purpura, petechiae, hemorrhage) i *infection *weight loss *bone pain, *liver, spleen and lymph node enlargement *elevated uric acid. abdominal pain, breast tenderness Acute Lymphoblastic Leukemia - -PATHOPHISIOLOGY: -aggressive, fast growing leukemia with too many lymphoblasts (immature WBCs) found in blood and bone marrow. -cause unknown but increased incidence with other hereditary abnormalities such Down's Syndrome, Trisomy 13, etc in children. -increased risk in adults linked to cigarette smoke, benzene, ionizing radiation. -Chromosomal alterations in ALL cause alterations of expression and function of transcription factors necessary for normal B and T-cell development. -CLINICAL MANIFESTATIONS bleeding (ecchymosis, purpura, petechiae, hemorrhage) -infection -weight loss -bone pain, -liver, spleen and lymph node enlargementmore common than in AML -elevated uric acid. -abdominal pain, breast tenderness
Chronic Lymphocytic Leukemia - -PATHOPHYSIOLOGY- most common chronic leukemia in adults in Western World. -slow growing cancer in which too many immature lymphocytes are found mostly in the blood and bone marrow. -Etiology unknown, familial tendency suggests genetic linkage; first-degree relatives have a 3 X greater risk for development. -rare in individuals younger than 45. -longer life expectancy, usually several years after DX in comparison to acute leukemias. -CLINICAL MANIFESTATIONS -advance slowly and insidiously -70% of patients are asymptomatic at the time of DX. -most common symptom, lymphadenopathy -most common effect, suppression of humoral immunity and increased infection w encapsulated bacteria. Chronic Myelogenous Leukemia - -PATHOPHYSIOLOGY Several forms, depending on the lineage of the malignant cells. -mostly a disease of adults but can occur in children or adolescents, peak incidence in 5th-6th decades of life. -longer life expectancy, usually several years after DX in comparison to acute leukemias. -Member of the family of myeloproliferative disorders. -clonal and thought to arise from a hematopoietic stem cell. -CLINICAL MANIFESTATIONS -advance slowly and insidiously -70% of patients are asymptomatic at the time of DX. -most common symptom, lymphadenopathy. -CML patients may progress through 3 phases of the disease: chronic phase lasting 2-5 years during which symptoms may bot be apparent, accelerated phase 6-18 months during which the primary symptoms (splenomegaly*painful) develop and terminal blast, w survival of only 3-6 months. Hodgkin Lymphoma - PATHOPHYSIOLOGY -malignant, progresses from one group of lymph nodes to another and includes the development of systemic symptoms and the presence of B cells called Reed-Sternberg (RS) cells. -higher incidence in males -median age 64 -RS cells represent malignant transformed lymphocytes, hallmark and necessary for DX. -may be linked to EBV. -CLINICAL MANIFESTATIONS -adenopathy. Mediastinal mass, splenomegaly, abdominal mass -fever, weight loss, night sweats, pruritus -labs:thrombocytosis, leukocytosis, eosinophillia, ESR, elevated alkaline phosphatase, paraneoplastic syndromes Non-Hodgkin Lyphoma - -PATHOPHYSIOLOGY
-CLINICAL MANIFESTATIONS
-in infants, may present as icterus neonatorum -most common, acute hemolytic anemia, usually after infections or the ingestion of certain oxidative drugs. -hemolytic episodes are characterized by pallor, icterus, dark urine, back pain, and in severe cases, shock, cardiovascular collapse and death. -b/w episodes, the child does not have anemia and erythrocyte survival is normal. Sickle Cell Anemia - -PATHOPHYSIOLOGY -a group of disorders that affects hemoglobin characterized by the presence of atypical forms of hemoglobin. -a mutation in the genes that encode hemoglobin -RBC that contain homozygous hemoglobin S mutation get the disease. -Sickled RBCs are unable to transport O2 effectively and stick together, blocking small blood vessels (vascular occlusion.) -more common among those with ancestors from Africa. -CLINICAL MANIFESTATIONS -much variation in the clinical manifestations. -some have mild symptoms, others have repeated vaso-occlusive crises. (pain crisis.) -general manifestations of hemolytic anemia: pallor, fatigue, jaundice, irritability. -vaso-occlusive crises-hypoxic injury that leads to infarct that is very painful in affected areas. -acute chest syndrome-high risk type of vaso-occlusive crisis involving the lungs. Presents w fever, cough, chest pain and accumulation of lung infiltrates. Hemophilias - A group of hereditary bleeding disorders that result from deficiencies of specific clotting disorders -PATHOPHYSIOLOGY Normal sequence of blood clotting requires more than 10 factors. The two missing factors in hemophilia: Factor 8 or antihemophilic factor, factor 9 or plasma thromboplastic component. Normal levels of factor 8 and 9 are 50% to 150%. -CLINICAL MANIFESTATIONS: Blood in urine or stool Joint pain and swelling Unexplained, excessive or easy bleeding Large and deep bruises Frequent nosebleeds Bleeding gums Irritability (especially in children)
