97 terms

Grump: Pathophysiology unit 1

Cellular adaptations, neoplasia, stages of wound healing, inflammation, and cancer
1. cells and tissue organs decrease in size or number
2. Cellular atrophy = cell loss
3. Causes: decrease in work demand or adverse work conditions
4. Decrease in function, increase in efficiency by decrease oxygen consumption and decrease in cellular processes
Organ Atrophy
1. irreversible loss of cells
ie) brain atrophy alzheimers
5 Categories of Cellular Atrophy
1. Disuse - decrease in workload or adverse environmental demands
2. denervation - occurs in paralyzed limbs that results from nerve damage
3. decrease in endocrine stimulation
4. malnutrition
5. loss of blood flow - ischemia
1. increase in cell size and increase in functioning tissue mass
2. Due to increase in workload and increase in function
ie) Normal Physiologic Hypertrophy - increase in muscle with increase in exercise
Pathologic Hypertrophy
1. abnormal hypertrophy
2. Adaptive Pathologic Hypertrophy - myocardial hypertrophy due to valvular disease or hypertension
3. Compensatory Pathologic Hypertrophy - enlargement of remaining organ or tissue after a portion has been removed.
1. increase in number of cells in organ tissue
2. Occurs in highly mitotic cells
Physiologic Compensatory Hyperplasia
occurs in response to hormonal or increase in functional demands (compensatory)
ie) regeneration of the liver
Non-Physiologic Hyperplasia
due to excessive hormonal stimulation or effects of growth factors on target tissues
ie) excessive estrogen production causes breast tissue cells to increase during pregnancy
1. reversible change in which one adult cell type is replaced with another cell type
2. Caused by chronic irritation and inflammation
3. Normal function
4. has adapative and non-adaptive responses
ie) Smoker's cough, tracheal lining is replaced with simple squamous epithelium (flat, no mucous, no cillia)
1. deranged cell growth of specific tissue that results in cells varying in size, shape, and appearance.
2. Due to chronic inflammation and irritation
3. Occurs after metaplastic cells have formed
4. strong indicator of cancer
5. adaptive which can be reversible
ie) cervical dyplasia due to HPV
1. programmed cell death
2. Removes cells that are being replaced or have "worn out"
3. Part of normal cellular process
1. cell death in organ or tissue that is still part of a living person
2. Unregulated death caused by injuries to cells
3. Cells swell and rupture
4. Inflammation results
Causes of Cell Injury
1. Hypoxia (lack of O₂) - caused by ischemia, respiratory disease, ↓ O₂ in air (↑ elevations), anemia, edema results in ATP depletion
2. Physical Agents - body impact, extreme temps, electrical forces results in neural or cardiac damage
3. Chemical Agents and Drugs - lead or alcohol
4. Biologic Agents - bacteria, fungus
5. Ionizing Radiation - free radicals that result in ionization of molecules in cells.
6. Nutritional Imbalances
Mechanisms of Cell Injury
1. ATP depletion - causes acute cellular edema H₂O and Na⁺ intracellular accumulation
2. Free Radical Injury - damages cell membranes, cross unit proteins, and inflammation processes and causes chain reactions
3. Impaired Ca²⁺ Homeostasis - Ca²⁺ may activate enzymes at the wrong time
Free Radicals
1. molecules with an unpaired electron in outer electron shell
2. extremely unstable and reactive
3. can damage normal cells and into them into free radicals
4. can be removed by antioxidants like Vitamin A, E, and C
Effects of Impaired Calcium homeostasis
1. usually maintained at a low intracellular level
2. can activate enzymes that will destroy cell
3. open more Ca²⁺ gates causing more Calcium to flow into cell
Process of Apoptosis
1. cells turn on their own enzymes, caspases
2. digest their own cell proteins and DNA
3. destroy by macrophages
Apoptosis can be caused by
1. Signaling factor attached to death domains on cell surface receptors
2. mitochondrial damage
3. protein, p53, activated by DNA damage
Dry Gangrene
1. lack of arterial blood supply but venous flow can carry fluid out of tissue.
2. tissue tends to coagulate - gel like substance
large area of necrotic tissue
Wet Gangrene
1. lack of venous flow lets fluid accumulate in tissue
2. tissue tends to liquefy and infection may spread
Gas Gangrene
1. caused by Clostridium infection which produces toxins and H₂S bubbles
2. occurs after wet gangrene
Signs of Inflammation
1. Rubor - redness
2. Dolor - pain
3. Tumor - swelling or edema
4. Calor - heat
5. loss of function
1. automatic response to cell injury that neutralizes agents, and removed dead tissue
Vascular Inflammation
1. Prostaglandins and leukotrienes affect BV
2. arterioles and venules dilate - ↑ blood flow causes redness and heat
3. capillaries become more permeable - exudate leaves tissue causing swelling and pain
Cellular Inflammation
1. leukocytes enter injured tissues and destroys infectious agents, removes damaged cells, releases more inflammatory mediators to control inflammation and healing
1. first attackers
2. most abundant
3. secrete H₂O₂ and N₂O₃
4. Kills pathogens
Band Cells
immature neutrophils
1. responds to allergic reactions and parasitic worms
2. controls release of chemical mediators
1. contains histamine and IgE (allergic reasponses)
2. develops into mast cells
Mast Cells
1. differentiated basophils in tissue
1. lives the longest and is largest WBC
2. signals immune response
3. resolves inflammatory response
1. phagocytic eaters
2. lives within tissue
3. acts as signaling device for other cells, APC
4. Differentiated monocyte in tissue
Systemic Signs of Inflammation
1. Fever
2. Lethargy (fatigue)
System Response of Inflammation
1. WBC response
2. Acute Phase Response
WBC Response
1. WBC enter injured area
2. WBC express adhesive proteins - platelet activating factors
3. attach to BV lining
5. squeeze between cells
6. follows inflammatory mediators to injured area - release histaimine, seratonin, and cytokines to further inflammation and vasodilation
Acute Phase Response
1. WBc release interleukins and tumor necrosis factor
2. affects thermoregulatory center in hypothalamus - causes fever
3. affects CNS - causes lethargy
4. skeletal muscle breakdown - makes amino acids for immune response and tissue repair
5. Liver makes Fibrinogen and C reactive Protein - causes clotting, binds pathogens, and moderate inflamm. response.
C-reactive Protein
1. binds to surface of microorganisms and targets for destruction by complement or phagocytosis
2. indicator of cardiovascular disease
Mechanisms to Heat Loss
1. contraction of pilomotor muscles - ↓ surface area for heat
2. ateriovenus shunts - allows blood to move form arterial to venus systems
open shunts - release heat, closed shunts trap heat
3. Blood volume - ↑ volume releases more heat, ↓ volume traps heat
4. Radiation and Conduction of skin through evaporation of sweat and insensible perspiration, exhalation of air, urine, and feces
Intermittent Fever
1. returns normal after 24 hours
2. caused by gram +/- bacteria, sepsis, absesses, and acute endocardial endocarditis
Remittent Fever
1. does not return to normal, varies between degrees
2. caused by legionella and mycoplasma infections
Sustained Fever
1. temp remains above normal with minimal variations
2. caused by drugs
Relapsing Fever
1. 1 or more episodes of fever
2. caused by TB, fungal infections, lime disease, and malaria
1. migration, proliferation, and differentiation of epithelial cells at the wound site to replace injured cells and tissue.
2. requires moist vascular environment - granulation tissue
Proud Flesh
1. excessive granulation tissue which may prevent epithelialization
2. accumulation of too much collagen and fibroblasts
1. abnormality as a result of impaired wound healing
2. tumor like masses caused by excess production of scar tissue
Growth Factor
proteins that stimulate proliferation, differentiation, and growth of cells.
1. transfer of disease from one organ or part to another that is not directly connected.
What causes cells to sickle?
deoxygenation - ↓O₂
increased exercise.
respiratory diseases,
high elevated areas,
What does Vitamin K Synthesize?
Clottings Factors: VII, IX, X
What steps of the Coagulation Cascade that does not require Factor IV, Ca²⁺?
steps 1 and 2 in the intrinsic system
Phases of Repair
1. Angiogenesis by FGF and VEGF through vasodilation
2. laying down of granulation tissue
3. building of ECM by emigration of fibroblasts - by deposition of collagen
4. degradation of some collagen by collagenase enzymes to remodel tissue
Phases of Wound Healing
1. Inflammatory Phase
2. Proliferative Phase
3. Remodeling Phase
Inflammatory Phase
1. begins with hemostasis and vasoconstriction
2. Platelet formation and aggregation
3. vascular stage begins to cause vasodilation
4. cellular stage is initiated to bring in WBC
Proliferative Phase
1. Fibroblasts and endothelial cells lay down granulation tissue
2. epithelialization occurs to form epithelial cells
Remodeling Phase
1. fibroblasts lay down more collagen and collagenase enzymes lysis collagen to build tissue with tensile strength
Primary Intention
1. sutured or surgical incision
2. small incision, ie) paper cut
3. could progress to 2° intention
Secondary Intention
1. larger wounds which have a greater loss of tissue and contamination
2. more susceptible to bacterial infection
3. undergo scar tissue formation
Benign Neoplasms
1. composed of well differentiated cells
2. slow progressive rate of growth
3. expand and remain localized in tissue of origin
4. lack capacity to metastasize
5. develops a fibrous capsule - line of demarcation
6. do not undergo degenerative changes
Malignant Neoplasms
1. lack differentiation
2. rapid rate of growth
3. ability to invade surrounding tissue and metastasize
4. tendency to compress BV, outgrow blood supply, liberate enzymes and toxins that destroy all tissue
Paraneoplastic Syndromes
1. manifestations not directly affected by cancer
2. cancer cells that produce hormones or hormone like proteins
3. common hormones, ADH (H₂O retention), ACTH (Adrenocorticotropic Hormone) (cushing's syndrome), PTH (↑ osteoclast activity to dissolve bone), clotting proteins
4. earliest indication of cancer
1. normal genes that code for normal proteins used in cell division
2. includes GF, GF receptors, G proteins, enzymes that produce 2nd messengers, regulatory proteins
Tumor Suppressor Proteins
1. stop the division of mutated cells
2. prevents cancer
3. include: cyclins, cyclin dependent kinases, Cyclin inhibitor (p53)
Phases of Onocogenesis
1. Initiation
2. Promotion
3. Progression
initial mutation occurs due to carcinogenic agents
1. mutated cells are stimulated to divide
2. induction of accelerated growth in an already initiated cell
3. is reversible if promoter is removed
1. tumor cells compete with one another and develop more mutations which make them more aggressive.
2. acquire malignant phenotypic changes - invasiveness, metastasis, competence, and autonomous growth tendencies
3. ↑ in karyotypic instability.
Steps of Metastasis
1. has to be able to break off and move
2. invades surrounding ECM
3. access to BV or lymph vessels
4. survive the journey
5. invade favorable location
6. grow via angiogenesis
Grading of Tumors
1. looking at histologic cellular characteristics
2. microscopic study that determines level of differentiation
3. I = most differentiated (benign), IV = least differ. (malignant)
Staging of Tumors
1. based on clinical spread or metastasis
2. T = size of tumor (1 = smallest, 4 = biggest)
3. N = node of involvement (0 = no nodes, 3 = multiple nodes)
4. M = metastasis (0 = no, 1 = yes)
neutrophil depletion either by ↓ production or ↑ destruction
What is the common cause of Neutropenia?
chemotherapy drugs due to cancers - suppress bone marrow stem cells
1. mutated proto-oncogenes
2. still code for proteins needed for cell division
3. may produce too much proteins, abnormal proteins, proteins that turn on by themselves, make proteins that are not needed, proteins that cannot turn off cell division, and protein that should be made by a different cell.
1. vascular spasm - vasoconstriction
2. platelet plug formation - adhesion and aggregation of platelets
3. coagulation cascade
4. clot retraction - closing clot
5. clot dissolution - fibrinolysis
Hodgekin Lymphoma
1. cancer of the peripheral lymph organs, typically above diaphragm usually painless
2. presence of Reed-sternberg cells (malignant B-cells)
3. metastasis typically spreads contiguously between lymph nodes
4. causes immunosuppression ↑ susceptibility of bacterial, fungal, and viral infections, anergy, ↑ neutrophil count, and anemia
5. Treatment includes irradiation and chemotherapy
6. cure rate of 85% within 5 yrs.
Non-Hodgekin Lymphoma
1. cancer of the lymphocytic cells affecting B and T cells within peripheral lymph tissue
2. may be due to impairment of immune and infectious agents
3. non-contiguous spread to other areas like liver, spleen, and bone marrow
4. ↑ susceptibility to infections, and poor ab response
5. 5th most common
6. 60-80% remission
Acute Lymphocytic Leukemia (ALL)
1. cancer of the Lymphocytic stem cells resulting ↑ neoplastic cells and ↓ in other cells with rapid onset
2. causes anemia, ↑ metabolism, splenomegaly, hepatomegaly, thrombocytosis, lymphadenopathy
3. symptoms: fever, night sweats, fatigue, weight loss, bone pain, and bleeding
4. treatment: induction therapy, intensification therapy, and maintenance therapy aimed for remission.
Chronic Lymphocytic Leukemia (CLL)
1. cancer of the lymphocytic stem cells proliferation of neoplastic B cells and T cells (well differentiated)
2. lymphocytosis, lymphadenopathy, splenomegaly, autoimmune hemolytic anemia and immune-mediated thrombocytopenia.
3. symptoms: fatigue, ↓exercise capacity, enlargement of superficial lymph nodes, splenomegaly, recurrent infections, pallor, edema, and vein inflammation
4. treatment: chemotherapy, monoclonal antibodies, corticosteroids, or splenectomy
Acute Myelogenous Leukemia (AML)
1. rapid proliferation of neoplastic myelogenous stem cells
2. strongly linked to toxins, underlying hematologic and congenital disorders
3. associated with Down Syndrome
4. symptoms: fatigue, low grade fever, night sweats, weight loss, bleeding, bone pain, and infections
5. treatment: induction therapy, intensification therapy, and maintenance therapy aimed for remission.
Chronic Myelogenous Leukemia (CML)
1. cancer of the myelogenous stem cells
2. associated with Phila. Chromosome and translocation of 9 and 22.
3. triphasic course: variable chronic phase symptoms of weakness and weight loss, short accelerated phase splenomegaly and increased basophil count, terminal blast crisis phase that develops into AML causing progressive splenomegaly, fever, weight loss, bone pain, and night sweats.
4. treatment: maintain blood counts, cytogenic response to destroy or reduce Philadelphia chromosome, molecular response to destroy BCR-ABL fusion protein, Chemotherapy and alpha interferon
Multiple Myeloma (MM)
1. proliferation of maligant plasma cells in bone marrow and osteolytic lesions (plasma cell dyscrasia)
2. causes pathologic bone fractures, hypercalcemia, hyperviscosity, ↑ infections due to ↓ in IgG, and heart failure
3. diagnosis: 1. bone marrow cytosis, 2. lytic bone lesions - unregulation of M proteins, 3. presence of M proteins and Bence-jones proteins in urine
4. associated with Asian Orange
5. Symptoms: Bone pain
6. Treatment: Chemo and radiation
Hemophilia A
1. X link recessive disorder that causes an abnormally low production of Coagulation factor VIII
2. commonly found in males
3. causes excessive bleeding, joint inflammation, fibrosis, contractures, muscle hematomas, GI tract and joint bleeding and intercranial hemorrhages that can result in death
4. Treatment: replacement Therapy of Factor VIII from human plasma and Desmopressin Acetate (stimulates release of vWF)
von Willebrand Disease
1. autosomal recessive trait that causes a deficiency or defect in von Willebrand Factor (vWF) which results in poor platelet adhesion
2. causes bruising, excessive menstrual bleeding, epistaxis,and bleeding in GI tract, joints, and mouth
3. Treatment: Replacement of Factor VIII with vWF and Desmopressin Acetate (stimulates release of vWF)
Disseminated Intravascular Coagulation (DIC)
1. overacting of clotting factors
2. occurs as a complication of another condition
3. begins with activation of coagulation sequence with unreg. generation of thrombin, forming fibrin
4. causes ↓ anticoagulants
5. thrombosis can occur causing organ failure, and clot formations use up all CF causing excessive bleeding
6. common conditions: obstetric disorders (pregnancy), trauma, sepsis, shock, infections, and cancer.
1. ↓ in platelet levels caused by ↓ production or ↑ destruction, or used up in clot formation
2. due to congenital or acquired anemia
3. common sites of bleeding: skin, mucous membranes, nose, mouth, and uterine tissue
4. caused by bone marrow disease, aplastic anemia, HIV, radiation and drugs
1. ↑ platelet #, ↑ platelet aggegration, endothelial damage, ↑ procoagulant factors, ↓ anticoagulatant factors
2. predisposes to thrombosis
Conditions associated with Hypercoagulability
1. smoking
2. atherosclerosis
3. diabetes mellitus
4. elevated lipid and cholesterol levels
5. thrombocytosis
Conditions that accelerate Coagulation Activity
1. pregnancy and puerperium (postpardom)
2. oral contraceptives
3. post surgical state
4. immobility
5. CHF
6. malignant diseases
What type of complications occur when a patient is given Heparin?
1. Thrombocytopenia which causes hemorrhaging and excessive bleeding
Symptoms associated with deficient O₂ capacity
1. anemias - hemolytic anemias and iron deficiency arnemias
2. hypoxia (↓ O₂ in tissue)
1. ↑ levels of unconjugated bilirubin, especially in neonates
2. ↑ RBC destruction, ↓ conjugation in liver
3. causes: breast feeding, hemolytic disease of newborn, hypoxia, infections, acidosis
4. results in kernicterus, lethargy, behavioral changes, ataxia (uncoordinated muscle movement), tremors, hearing loss, retardation, and seizures
5. treatment: phototherapy
What results in ↑ RBC destruction? What is the compensation?
1. ↑ unconjugated bilirubin - causing jaundice
2. ↑ hemoglobin levels, ↓ haptoglobin levels
3. compensations: splenomegaly, hepatomegaly, bone marrow expansion
1. group of auto-recessive disorders affecting beta and alpha hemoglobin chains
2. lead to abnormal RBC production and oxygen free radicals causing anemia and hemolysis
3. causes Heinz bodies, strokes, pulmonary embolisms, anti/pro-coagulant imbalances, and endothelial activation
4. Symptoms: enlarged facial bones, splenomegaly, bone fractures and thinness
5. Treatment: life-long blood transfusions, monitored for infections, iron chelation therapy, daily doses of folic acid, regular checks of heart and liver function, bone marrow transplants, splenectomy, and possible removal of the gallbladder
Sickle Cell Anemia
1. inherited recessive disorder causing the abnormal formation of S hemoglobin of Beta globin chains.
2. Cells sickle due to deoxygenation
3. causes clumping of cells and rigidity
4. symptoms: ischemia, infarctions, obstruction, acute pain in chest, abdomen, joints, bones, spleen injuries
5. common complication: Acute Chest Syndrome due to pulmonary infarction
6. Treatment: for infections, blood transfusions, cytoxic drugs, hydroxyurea
yellow discoloration due to accumulation of unconjugated bilirubin in the blood.
Contributions to Blood Viscosity
1. RBC production
2. platelet aggregation
3. temperature (cold = ↑ viscosity)
Two Patterns of Reversible Cellular Injury
1. cellular swelling - caused by Hypoxia, edema of cellular organelles due to ↑ Na⁺ levels in ICM. Causes ↓ protein synthesis and energy production. Once stimulus is removed, tissue returns to normal state
2. Fatty changes in tissue - fatty depositions throughout cytoplasm due to ↑ fat load or ↓ metabolism of fats. Accumulation of fat in the liver results.