Lecture 2: Cell Pathology Flashcards
Anatomy of a Cell:
- Nucleus
- Cytoplasm:
I. Mitochondria
II. Ribosomes
III. Endoplasmic Reticulum
IV. Golgi Apparatus
V. Lysosome - Plasma Membrane
Nucleus
Contains RNA and DNA arranged together called chromatin (our genetic material)
Contains other proteins
Contains a nucleolus
Where mitosis happens: duplication of these cells
Cytoplasm
The liquid interior of a cell that houses many organelles. Also contains a cytoskeleton that forms scaffolding or framework for the cell.
- Mitochondria
- Ribosomes
- Endoplasmic Reticulum
- Golgi Apparatus
- Lysosome
Cytoplasm - Mitochondria
Involved in the generation of energy by cellular respiration and the formation of adenosine triphosphate (ATP).
Liver and nerve cells require lots of energy so have lots of mitochondria
Cytoplasm - Ribosomes
Composed of small granules of RNA floating freely or attached to the rough endoplasmic reticulum. Involved in protein synthesis (structural proteins and enzymes) so very important for maintenance of basic cell functions.
Cytoplasm - Endoplasmic Reticulum
A meshwork of membranes that are continuous
with the outer plasma membrane on one side and
the nuclear membrane on the other side.
Smooth: catabolism of drugs , hormones (steroids) and other nutrients
Rough: site of protein synthesis
Cytoplasm - Golgi Apparatus
Composed of tubules and cisternae adjacent to nucleus. Proteins produced in the smooth endoplasmic reticulum (SER) pass through the golgi apparatus where they are biochemically modified and then packaged into lysosomes
Cytoplasm - Lysosome
Membrane bound digestive enzymes called acid hydrolases are packaged into this organelle. They originate in the golgi apparatus.
Cytoplasm - Cytoskeleton
Lies in between the organelles (bào quan) and in the cytoplasm (tế bào chất
Maintains cell shape and helps cell adapt to mechanical pressure.
Helpful in movement of the cell.
Composed of a network of three differing filaments:
- Microfilaments-actin and myosin
- Microtubules-tubulin, also help form mitotic spindles during cell division
- Intermediate filaments-variable
Plasma Membrane
Forms the outer surface of the cell. It is composed of proteins, lipids, carbohydrates all arranged in a complex bilayer. It is a living structure maintained constantly and requiring energy (ATP).
Normal Cell Function:
Chemical signalling occurs through interaction with other cells in the body.
- Autocrine stimulation: self stimulation
- Paracrine stimulation: from one cell to another
- Endocrine stimulation: from somewhere else in the body via the bloodstream
Homeostasis: definition
The state of balance in a cell or equilibrium “steady state”.
Balance between all things that affect the cell like pressures, nutrients, oxygen, carbon dioxide, wastes, hormones and essential minerals.
The cell functions at optimum when in equilibrium.
Cell Functions in response to injury:
If the changes in the cell are within the normal range of homeostasis the changes are reversible. If the changes are too great they are irreversible.
Cells can change in size, in number and in their form or shape.
Reversible Cell Injury
Typically mild and short lived.
Reversible cell injury causes:
- decreased energy production
- decreased protein synthesis
- increased autophagy or “self eating”.
These changes are minor so are reversible.
Irreversible Cell Injury
Typically more severe and longer lasting damage.
The damage is greater, so homeostasis can not be achieved.
Structural changes in the cell:
- Loss of cell integrity and the cell membrane ruptures and the contents of the cell is released into the extracellular fluid, the cell dies.
- Mitochondria production has fallen below the essential minimum and can not be restored, the cell dies
Causes of Cell Injury
- Hypoxia (less oxygen) & anoxia (no oxygen)
- Ischemia & deprivation thiếu thốn of essential nutrients
- Toxic injury
- Microbial pathogens Vi sinh vật gây bệnh
- Mediators of inflammatory & immune reactions (inappropriate immune response)
- Genetic & metabolic disturbances rối loạn trao đổi chất (genetic error or enzyme defects
Causes of Cell Injury:
- Causes of Cell Injury: Lack of Oxygen
Hypoxia - reduced amount of oxygen available
Anoxia - no amount of oxygen available
Most common cause of cell injury. Short term oxygen deprivation is often reversible, but long term is not. Oxygen is essential for cellular respiration, with no oxygen there is no energy production (ATP) and the cell dies.
Tissues most affected: brain, heart, kidney
Tissues least affected: connective tissues
Causes of Cell Injury:
- Ischemia & deprivation of essential nutrients thiếu thốn
This is a restriction in blood supply that causes loss of oxygen and also all other nutrients.
Causes of Cell Injury:
- Toxic injury
Direct toxic effect on cells.
eg/ heavy metals like Mercury inactivate enzymes
Indirect toxic effect on cells: it needs to be metabolized first
eg/ dry cleaning chemicals: produces free radicals and damages cell membranes
Many pharmaceutical drugs have toxic effects in large doses and may be lethal
eg/ each drug affects cells and organs differently
Causes of Cell Injury:
- Microbial pathogens
Bacteria often produce toxins that may inhibit many cell functions.
eg/ food poisoning happens when endotoxins produced by spoiled food become toxic to our gastrointestinal cells causing nausea, vomiting and diarrhea.
Viruses invade cells and kill from within, disturbing many cellular functions, if they don’t kill the cells they mark the cells as “invaded” and the immune system comes along and kills the invaded cell for the virus.
Causes of Cell Injury;
- Mediators of inflammatory & immune reactions
Cytokines sự phân bào, interferons and the complement system all may injure cells. They are produced by the body in response to infection or other immune reactions, but may go too far and kill the body’s own cells
Causes of Cell Injury:
- Genetic & metabolic disturbances
Genetic diseases adversely affect cells and their metabolic processes, leaving a build up of toxic amounts of metabolic substances.
eg/ diabetes mellitus: caused by insulin deficiency, causes a build up of too much glucose in the blood, this alters the function of many organs (liver & kidney) and also causes microdamage to small blood vessels, causing hypoxia.
Cellular Adaptations
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Intracellular accumulations
- Aging
- Cell death
Cellular Adaptations:
- Atrophy
Denotes Biểu thị a decrease in the size of a cell, tissue or organ and therefore also reduced metabolic processes, reduced energy production in the cell and reducing the size of the tissue or organ.
Physiologic Atrophy: occurs with aging, involves entire body
Pathologic Atrophy: occurs from inadequate nutrition or oxygen supply
Cellular Adaptations:
- Hypertrophy:
denotes Biểu thị an increase in the size of individual cells
Cellular Adaptations:
- Hyperplasia:
denotes an increase in the number of cells that causes an increase in the size of tissues and organs
Cellular Adaptations:
Neoplasia:
denotes an increase in the growth of tissue, usually collects together and form tumours
Cellular Adaptations:
- Metaplasia
This is a change of one mature cell type into another mature cell type, even the function changes. This change is usually reversible.
eg/ with smokers, the columnar epithelial cells in the mucosal lining of the bronchioles change into stratified squamous epithelial cells when irritated by cigarette smoke. This thickens the respiratory epithelium and causes it to lose its ability of clearing mucus and other debris.
Dysplasia: an increase in numbers of cells and their rate of mitosis, abnormal size and shape
Anaplasia: this is where cells become less differentiated or de-evolve back into stem cells
Cellular Adaptations:
- Intracellular Accumulations:
Caused by overload of metabolites or inability to secrete excesses.
Anthracosis bệnh than : accumulations sự tích lũy of coal particles, cigarette smoke or any air pollution, effects lungs and bronchioles
Hemosiderosis: accumulations of hemosiderin, a brown pigment in our blood, from the breakdown of hemoglobin in our blood, causes liver damage and sclerosis xơ cứng
Lipid accumulation sự tích lũy : accumulations of lipids or fats, common in obesity and alcoholism
Cellular Adaptations:
- Aging: Gerontology Lão khoa
Many processes are happening continually and are mostly irreversible.
Two main theories on aging and cellular adaptation:
“Wear and Tear” hypothesis giả thuyết : especially in organs like the brain and heart where cells do not regenerate.
“Genetic” hypothesis: aging is a genetically predetermined process.
Overall most organs undergo atrophy and have some reduced function, also have a reduced resistance to infection, increases in cardiovascular diseases and cancer.
Cellular Adaptations:
- Cell Death
Every cell in our body has a finite life span, some are replaceable and some are not
Eg/ red blood cells live up to 120q (90-120) days whereas platelets live for only 5-10 days.
We have two types of cell death:
- Necrosis: caused by exogenous processes (outside the cell) like hypoxia, ischemia, physical agents, trauma, imbalances, infection, many types, effects groups of cells or entire organs.
- Apoptosis: caused by endogenous processes (inside the cell), the cell is programmed to die by its own DNA, effects single cells, cancer cells often have mutations that retard this process
Cellular Adaptations:
Cell Death: Necrosis:
Types
- Coagulative necrosis
- Liquefactive necrosis
- Caseous necrosis
- Fat necrosis
Cellular Adaptations:
Cell Death: Necrosis:
Types:
- Coagulative necrosis
- Most common
- Causes rapid inactivation of enzymes
- Involves solid internal organs (heart, liver or kidneys)
- Most often caused by anoxia (ischemia)
eg/ myocardial infarction (heart attack)
Cellular Adaptations:
Cell Death: Necrosis:
Types:
- Liquefactive necrosis
Tissues dissolve and become soft and mushy and liquefy due to enzymatic activity
Occurs often in the brain
Caused by a brain infarct (stroke) and produces a fluid filled cavity in the brain
Cellular Adaptations:
Cell Death: Necrosis:
Types:
- Caseous necrosis: Trường hợp hoại tử
Typically found in a patient with tuberculosis bệnh lao or fungal infections
Inside a granuloma, the necrotic cells fall apart
The tissue is yellow-white and cheesy looking
Cellular Adaptations:
Cell Death: Necrosis:
Types:
- Fat necrosis
A special kind of liquefactive necrosis hoại tử hóa lỏng
Lipolytic enzymes usually around the pancreas break down the accumulated lipids into glycerols and free fatty acids, these combine with calcium and form soaps
Associated with trauma to the pancreas or pancreatitis
Cellular Adaptations
Cell Death - Apoptosis
This is the pre-programmed form of cell death. It is already written in the genes of our DNA of every cell in our body and needs activating (these genes on the DNA are called “suicide genes”).
This process usually affects single cells. It is a highly regulated process occurring from birth to death.
May be induced by adverse exogenous events
Physiologic apoptosis: very important in the fetus when the body is forming, old cells must die for new more differentiated cells to be produced.
Pathologic apoptosis: caused by faulty tissues due to genetic or metabolic disorders, malformed không đúng hình dạng or dysfunctional cells die.
Lack of apoptosis: may also be pathological, eg/ syndactily, leukemia (wbc’s don’t die, they accumulate tích trữ and become dysfunctional)
Cells life span
Red blood cells - 120 days
White blood cells - 10 hours to decades
Platelets - 5-9 days
Extracellular Degeneration
Changes in the matrix
Changes in the fibres
* Fibrosis Xơ hóa
* Hyalinization of collagen
* Fibroid necrosis Hoại tử u xơ /necrobiosis bệnh hoại tử
Cellular Pathologies
I. Anemia’s: Red Blood Cells
1. Iron deficiency Anemia 2. Idiopathic Anemia 3. Pernicious Anemia 4. Folic Acid Anemia 5. Sickle Cell Anemia 6. Aplastic Anemia 7. Nutritional Anemia 8. Hemolytic Anemia 9. Hemorrhagic Anemia
II. Hemophilia: Red Blood Cells
III. Leukemia: White Blood Cells
Anemias in General
Description: All anemias are a reduction in quantity
and quality of red blood cells, or a component of
them like hemoglobin. This impairs the ability of
blood to carry oxygen and leads to hypoxia in tissues.
Anemias are classified by:
- red blood cell colour: hypochromic, normochromic, hyperchromic
- red blood cell size: microcytic, normocytic, macrocytic
- by causative factor: iron deficiency, folic acid deficiency, hemorrhagic, megaloblastic, aplastic
Iron Deficiency Anemia
Description: most common type of anemia, associated with depletion of iron in the body, this impedes cản trở hemoglobin synthesis, which then impedes oxygen transport. Affects 20% of all women and 50% of pregnant women and 3% of men.
Red Blood cells are small or microcytic
Idiopathic Anemia
Description: bone marrow stops making red blood cells for an unknown reason, causing widespread hypoxia.
Pernicious Anemia Thiếu máu ác tính
Description:
A lack of Vitamin B12 causes red blood cells to form
larger than normal. Because they still carry the same
amount of hemoglobin, these larger RBCs take up
more space but carry the same amount of oxygen so there is fewer of them in general, so less hemoglobin in general and less oxygen carrying capacity. These RBCs are destroyed prematurely so less of them.
Red Blood cells are larger than normal, macrocytic or megaloblastic
Folic Acid Deficiency Anemia
Description: a lack of folic acid in the blood.
Folic acid is used in making red blood cells,
if not enough folic acid then not enough
red blood cells, then anemia. It is also important in forming the neural tube in an embryo.
Red Blood Cells are larger than normal, macrocytic or megaloblastic
Sickle Cell Anemia Bệnh thiếu máu hồng cầu hình liềm
Description: a genetic disorder that causes a hemolytic tan máu anemia. RBCs are destroyed (called hemolysis) and their shape changes into a crescent or sickle shape. These misshapen cells live only 20 days instead of 120. They also have a tendency to get stuck and obstruct small blood vessels leading to hypoxia. Because of all of the above the blood has less oxygen carrying capacity, causing hypoxia also.
Nutritional Anemia
Description: caused by a lack of iron, protein, Vitamin B12, or other vitamins and minerals that are needed for the formation of hemoglobin. See Iron deficiency anemia and Folic Acid Deficiency Anemia.
Aplastic Anemia Thiếu máu không tái tạo
Description: a rare and life threatening type of anemia caused by a complete bone marrow failure. This lowers the numbers of red blood cells, white blood cells and platelets in the blood.
Three types of aplastic anemia: idiopathic, acquired (from cancer or toxins), hereditery vô căn, mắc phải (do ung thư hoặc chất độc), di truyền
Hemorrhagic Anemia Thiếu máu xuất huyết
Description: This anemia is the result of massive blood loss which may be accompanied by shock. A life threatening condition.
Hemolytic Anemia Chứng tan máu, thiếu máu
Description: red blood cells are destroyed (hemolysis) faster than they can be produced in the bone marrow and are also defective. Caused by a transfusion of mismatched blood. The antigens are foreign and treated as an invader and therefore destroyed. This impedes oxygen carrying capacity. There are less and less functioning red blood cells to carry oxygen.
Secondary Anemia
Description: also called the anemia of chronic disease. It is low levels of red blood cells due to some other chronic disease. Often in hospitalized patients, very common. Usually from defective iron incorporation during erythropoiesis. kết hợp sắt bị khiếm khuyết trong quá trình tạo hồng cầu
Anemias (thiếu máu)
Clinical Features: anemias have similar symptoms: fatigue, headache, chest pain, irregular heart beat, cold intolerance, shortness of breath, pallor xanh xao, dizziness, brittle hair, spoon shaped nails, delayed healing, swollen ankles, sore/beefy red tongue, cracked lips and intermittent từng cơn calf pain.
Hemophilia bệnh máu khó đông
I. Description: a genetic disorder that impairs clotting mechanisms in the blood. Allowing bleeding to continue with a loss of red blood cells.
Our blood contains 20 different clotting factors, a lack of just one prevents formation of a fibrin clot. There are 3 types:
A lack of any clotting factor prevents the formation of a stable fibrin clot
Three Types:
- In type A hemophilia, factor VIII is deficient
- In type B hemophilia, factor IX is deficient
- In type C hemophilia, factor XI is deficient
II. Etiology:
genetic cause, mutation in the gene that forms a clotting factor to form fibrin clots.
III. Pathogenesis:
mutated gene results in dysfunction or deficiency of clotting factors.
IV. Clinical Features: :
prolonged bleeding from minor injuries like a nose bleed or excessive bruising. Joint cavities may also bleed causing pain, swelling and stiffness. Symptoms may be mild, moderate or severe. Blood in urine or feces may result.
V. Treatment:
injected clotting factors
Leukemia Bệnh bạch cầu
I. Definition or description:
cancer of the blood forming tissues in our bone marrow and spleen. There is an uncontrolled accumulation of immature, dysfunctional white blood cells. These cells overcrowd in the bone marrow and in the bloodstream which causes a reduced production of functioning white blood cells. Cancerous white blood cells eventually spread throughout the body via lymph nodes and the bloodstream to the spleen, liver, brain and other organs. Death is usually from overwhelming infection.
4 TYPES:
- Acute lymphocytic leukemia (ALL)
- Chronic lymphocytic leukemia (CLL)
- Acute myelogenous leukemia (AML) Bệnh bạch cầu tủy cấp tính
- Chronic myelogenous leukemia (CML)
II. Etiology:
unknown, risk factors include: down’s syndrome, previous chemotherapy, exposure to chemicals and tobacco exposure.
III. Pathogenesis:
white blood cells are dysfunctional and overcrowd functional white blood cells in the body.
Clinical Features: persistent fatigue, shortness of breath, loss of appetite, weight loss, night sweats, bone pain, bleeding, petechiae đốm xuất huyết, frequent infection, enlarged lymph nodes, pale skin, enlarged liver or spleen.
IV. Treatment: chemotherapy, radiation therapy, stem cell transplant or a bone marrow transplant