General Principles Week 1 to 4 Flashcards
Topic 1 – Cell Adaptation and Cell Injury
TLO 1.1 Describe the types and mechanisms of cell adaptations with examples
Cell adaptation refers to the ability of cells to respond to various types of stimuli and adverse environmental changes. The four main types of cellular adaptations are:
- Hypertrophy: An increase in the size of individual cells. For example, enlargement of skeletal muscle cells due to exercise.
- Hyperplasia: An increase in the number of cells. For example, an increase in the number of epithelial breast cells during pregnancy.
- Atrophy: A reduction in cell size and number. For example, muscle atrophy due to disuse.
- Metaplasia: Transformation from one type of epithelium to another. For example, Barrett’s esophagus due to chronic gastric acid exposure.
These adaptations can be physiologic (normal) or pathologic (abnormal) depending on the stimulus. Cells adapt to maintain homeostasis and cope with new demands placed on them.TLO
1.2 Describe the types and causes of cell injury
Cell injury can be classified into two main types:
- Reversible cell injury: The cell can recover if the damaging stimulus is removed.
- Irreversible cell injury: The cell cannot recover and will die.
Causes of cell injury include:
**Hypoxia (Lack of Oxygen):
**Ischemia (reduced blood flow)
Anemia (reduced oxygen-carrying capacity of blood)
Carbon monoxide poisoning
**Physical Agents:
**Trauma (mechanical injury)
Extreme temperatures (heat or cold)
Radiation
Electric shock
**Chemical Agents and Drugs:
**Environmental toxins (e.g., pesticides)
Drugs and alcohol
Heavy metals (e.g., lead, mercury)
**Infectious Agents:
**Bacteria
Viruses
Fungi
Parasites
**Immunologic Reactions:
**Autoimmune diseases
Allergic reactions
**Genetic Factors:
**Inherited mutations
Chromosomal abnormalities
**Nutritional Imbalances:
**Deficiencies (e.g., vitamin, protein)
Excesses (e.g., obesity, hypervitaminosis)
**Aging:
**Accumulation of cellular damage over time
Reduced ability of cells to repair themselves
These factors can lead to different types of cell injury, depending on the severity and duration of the exposure. If you need more details about any specific cause, just let me know!
TLO 1.3 Discuss the pathogenesis and features of reversible and irreversible cell injury
Reversible cell injury:
- Characterized by cellular swelling due to failure of the sodium-potassium pump
- Accumulation of fatty acids in the cytoplasm (fatty change)
- Cellular functions are altered but can be restored if the injurious stimulus is removed
TLO 1.3 Discuss the pathogenesis and features of reversible and irreversible cell injury
Irreversible cell injury:
**Pathogenesis of Irreversible Cell Injury
**Membrane Damage
Mitochondrial Dysfunction
Calcium Influx
Reactive Oxygen Species (ROS) Production
Nuclear Changes
**Features of Irreversible Cell Injury
**Cellular Swelling
Loss of Membrane Integrity
Mitochondrial Damage
Nuclear Changes
Increased Calcium Levels
Lysosomal Enzyme Release
The transition from reversible to irreversible injury is marked by the inability to reverse mitochondrial dysfunction and extreme disturbances in membrane function.
TLO 1.4 Compare the cellular features of reversible and irreversible injury
Reversible injury features:
Fatty Changes
Mitochondrial Changes
Endoplasmic Reticulum (ER) Changes
Nuclear Changes
Cellular Swelling
Plasma Membrane Alterations
TLO 1.4 Compare the cellular features of reversible and irreversible injury
Irreversible injury features:
Irreversible injury features:
* Severe mitochondrial damage
* Extensive damage to plasma membrane
* Nuclear changes (pyknosis, karyorrhexis, karyolysis)
* Cytoplasmic blebs rupture
* Lysosomes rupture and release hydrolytic enzymes
The key difference is that in reversible injury, the basic cell structure remains intact and can recover, while in irreversible injury, there is a breakdown of cellular organelles and membranes leading to cell death.
Topic 2 – Irreversible Cell Injury
TLO 2.1 Describe the pathogenesis of different types of necrosis
Necrosis is a form of cell death characterized by cellular swelling, breakdown of organelles, and rupture of cell membranes. The main types of necrosis include:
**Coagulative Necrosis:
**
Pathogenesis: Occurs due to ischemia (reduced blood flow) leading to loss of blood supply. This results in protein denaturation, which preserves the basic cell outlines but makes the tissue firm.
**Liquefactive Necrosis:
**
Pathogenesis: Caused by enzymatic digestion of dead cells. Common in the brain due to its high lipid content and in abscesses due to bacterial infections. Results in a liquid, viscous mass.
**Caseous Necrosis:
**
Pathogenesis: Typically seen in tuberculosis infections. The immune response causes a combination of coagulative and liquefactive necrosis, resulting in a cheese-like appearance.
**Fat Necrosis:
**
Pathogenesis: Caused by the release of pancreatic enzymes that digest fat cells (e.g., in acute pancreatitis) or by trauma to fatty tissues. Results in chalky, white areas due to fat saponification.
**Fibrinoid Necrosis:
**
Pathogenesis: Occurs in immune-mediated diseases. Immune complexes and fibrin are deposited in vessel walls, causing a bright pink, fibrin-like appearance on microscopy.
**Gangrenous Necrosis:
**
Pathogenesis: Results from severe hypoxia, often due to ischemia. Can be classified as dry gangrene (coagulative) or wet gangrene (liquefactive) if secondary infection is present.
These pathogenesis mechanisms help explain how different types of necrosis occur and their distinct features.
TLO 2.2 Discuss the morphological features of different types of necrosis
**Coagulative Necrosis:
**Gross Appearance: Firm tissue
Microscopic Appearance: Cell outlines preserved (ghost-like cells), red appearance
**Liquefactive Necrosis:
**Gross Appearance: Liquid, creamy yellow (pus)
Microscopic Appearance: Many neutrophils and cell debris
**Caseous Necrosis:
**Gross Appearance: White, soft, cheesy material
Microscopic Appearance: Fragmented cells and debris surrounded by lymphocytes and macrophages (granuloma)
**Fat Necrosis:
**Gross Appearance: Chalky, white areas
Microscopic Appearance: Shadowy outlines of dead fat cells, sometimes bluish from calcium deposits
**Fibrinoid Necrosis:
**Gross Appearance: Changes too small to see grossly
Microscopic Appearance: Thickened vessel walls, pinkish-red deposits (fibrin-like)
**Gangrenous Necrosis:
**Gross Appearance: Black, dead skin; underlying tissue in varying stages of decomposition
Microscopic Appearance: Initially coagulative necrosis, followed by liquefactive necrosis if infected
TLO 2.3 Discuss the pathogenesis of apoptosis
Apoptosis is a programmed cell death process characterized by:
- Activation of caspase enzymes
- Chromatin condensation and DNA fragmentation
- Cell shrinkage and membrane blebbing
- Formation of apoptotic bodies
There are two main pathways of apoptosis:
- Extrinsic pathway: Triggered by external signals binding to death receptors on the cell surface.
- Intrinsic pathway: Initiated by internal cellular stress, leading to mitochondrial release of cytochrome c.
Both pathways converge on the activation of executioner caspases, which cleave cellular proteins and lead to cell death
TLO 2.4 List examples of physiologic apoptosis
- Embryonic development (e.g., formation of digits)
- Hormone-dependent involution (e.g., endometrial breakdown during menstruation)
- Cell turnover in continuously renewing tissues (e.g., intestinal epithelium)
- Immune system regulation (e.g., deletion of self-reactive T cells)
TLO 2.4 List examples of pathologic apoptosis
**Neurodegenerative Diseases:
**Alzheimer’s disease
Parkinson’s disease
Huntington’s disease
**Viral Infections:
**HIV/AIDS
Hepatitis B and C
**Cancer:
**Tumor regression after chemotherapy
Radiation therapy
**Autoimmune Disorders:
**Systemic lupus erythematosus (SLE)
Type 1 diabetes
**Ischemia-Reperfusion Injury:
**Myocardial infarction (heart attack)
Stroke
These are some situations where apoptosis, or programmed cell death, occurs pathologically and contributes to disease processes.
Topic 3 – Acute Inflammation
TLO 3.1 List the causes and cardinal signs of inflammation
Causes of inflammation:
**Infections:
**Bacteria
Viruses
Fungi
Parasites
**Physical Injury:
**Trauma
Cuts and wounds
Burns
Frostbite
**Chemical Agents:
**Toxins
Irritants
**Immune Reactions:
**Autoimmune diseases (e.g., rheumatoid arthritis)
Allergies (e.g., pollen, pet dander)
**Foreign Bodies:
**Splinters
Dirt
Surgical sutures
**Chronic Conditions:
**Obesity
Chronic infections (e.g., tuberculosis)
**Tissue necrosis
**
Cardinal signs of inflammation (5 classical signs):
Calor (heat)
Dolor (pain)
Rubor (redness)
Tumor (swelling)
Functio laesa (loss of function)
TLO 3.2 Discuss the vascular and cellular events in inflammation
Vascular events:
Vascular events:
1. Vasodilation: Increased blood flow to the affected area
2. Increased vascular permeability: Allows plasma proteins and fluid to enter
TLO 3.2 Discuss the vascular and cellular events in inflammation
Cellular events:
Cellular events:
1. Margination: Leukocytes line up along vessel walls
2. Rolling: Leukocytes roll along endothelium
3. Adhesion: Leukocytes firmly attach to endothelium
4. Transmigration: Leukocytes move through vessel walls into tissues
5. Chemotaxis: Directed movement of leukocytes towards the site of injury
6. Phagocytosis: Ingestion and destruction of microbes and debris
TLO 3.3 Discuss the mediators and outcomes of acute inflammation
Mediators of inflammation:
These mediators work together to produce the signs and symptoms of inflammation, such as redness, heat, swelling, pain, and loss of function.
- Vasoactive amines (e.g., histamine)
- Plasma proteins (e.g., complement, kinins)
- Lipid mediators (e.g., prostaglandins, leukotrienes)
- Cytokines (e.g., TNF-α, IL-1)
- Chemokines
- Nitric oxide
Histamine:
Released by mast cells and basophils
Causes vasodilation and increased permeability of blood vessels
Prostaglandins:
Produced from arachidonic acid
Cause vasodilation, pain, and fever
Cytokines:
Small proteins released by immune cells
Include interleukins (IL), tumor necrosis factor (TNF), and interferons (IFN)
Regulate immune and inflammatory responses
Leukotrienes:
Produced from arachidonic acid
Cause increased permeability of blood vessels and attract white blood cells (chemotaxis)
Bradykinin:
A peptide that causes vasodilation and increases permeability of blood vessels
Causes pain and smooth muscle contraction
TLO 3.3 Discuss the mediators and outcomes of acute inflammation
Outcomes of acute inflammation:
Outcomes of acute inflammation:
1. Resolution: Complete restoration of normal tissue structure and function
2. Fibrosis: Replacement of damaged tissue with scar tissue
3. Abscess formation: Localized collection of pus
4. Chronic inflammation: Persistent inflammatory response
TLO 3.4 Describe the morphological features of acute inflammation
Morphological features of acute inflammation include:
1. Vascular changes:
- Vascular changes:
* Vasodilation
* Increased blood flow
* Vascular congestion
TLO 3.4 Describe the morphological features of acute inflammation
Morphological features associated with each of these aspects of acute inflammation:
**Vascular Changes:
**Vasodilation:
**Blood vessels widen, leading to increased blood flow.
Causes redness and warmth in the affected area.
**Increased Vascular Permeability:
**Blood vessel walls become more permeable.
Plasma proteins and fluids leak into the surrounding tissue.
Edema:
Fluid Accumulation:
Result of increased vascular permeability.
Causes swelling due to the accumulation of fluid in tissues.
Cellular Infiltrate:
Leukocyte Migration:
White blood cells (mainly neutrophils) move out of blood vessels into the inflamed tissue.
Involves rolling, adhesion, and transmigration of leukocytes.
**Phagocytosis:
***
Immune cells engulf and digest pathogens and debris.
**Fibrin Deposition:
Fibrin Formation:
Fibrinogen leaks from blood vessels and is converted to fibrin.
Fibrin forms a mesh-like structure in the tissue.
Tissue Necrosis:
Cell Death:
Severe or prolonged inflammation can lead to cell injury and death (necrosis).
Accumulation of dead cells and debris in the inflamed area.
These features collectively contribute to the signs and symptoms of acute inflammation, such as redness, heat, swelling, pain, and loss of function.
TLO 3.4 Describe the morphological features of acute inflammation
3. Cellular infiltrate:
- Cellular infiltrate:
* Predominance of neutrophils in early stages
* Later influx of macrophages and lymphocytes
TLO 3.4 Describe the morphological features of acute inflammation
4. Fibrin deposition:
- Fibrin deposition:
* Formation of fibrin networks in exudates
TLO 3.4 Describe the morphological features of acute inflammation
TLO 3.4 Describe the morphological features of acute inflammation
5. Tissue necrosis:
- Tissue necrosis:
* In severe cases, localized tissue destruction
Specific patterns of acute inflammation include:
- Serous inflammation: Protein-rich fluid exudate
- Fibrinous inflammation: Exudate rich in fibrin
- Suppurative (purulent) inflammation: Formation of pus
- Ulcers: Local defects in surface epithelium
Topic 4 – Chronic Inflammation and Wound Healing
TLO 4.1 Describe the pathogenesis and morphological features of chronic inflammation
Pathogenesis of chronic inflammation:
Pathogenesis of chronic inflammation:
* Persistent infection
* Prolonged exposure to toxic agents
* Autoimmune reactions
* Recurrent acute inflammation
TLO 4.1 Describe the pathogenesis and morphological features of chronic inflammation
Morphological features:
- Cellular infiltrate: Predominance of mononuclear cells (lymphocytes, plasma cells, macrophages)
- Tissue destruction: Ongoing damage due to inflammatory mediators
- Repair: Attempts at healing through fibrosis and angiogenesis
- Granulation tissue formation: New blood vessels and fibroblasts
- Fibrosis: Excessive collagen deposition leading to scarring
TLO 4.2 Discuss the morphological features of granulomatous inflammation
Granulomatous inflammation is characterized by:
Granulomatous inflammation is characterized by:
1. Formation of granulomas: Focal collections of activated macrophages
2. Epithelioid cells: Modified macrophages with abundant pink cytoplasm
3. Multinucleated giant cells: Fusion of epithelioid cells
4. Lymphocyte cuff: Surrounding the granuloma
5. Central necrosis: In some cases (e.g., tuberculosis)
6. Fibrosis: Surrounding the granuloma in later stages
Types of granulomas:
- Foreign body granulomas
- Immune granulomas (e.g., tuberculosis, sarcoidosis)
TLO 4.3 Enumerate the complications and factors affecting wound healing
Complications of wound healing:
Complications of wound healing:
1. Excessive scarring or keloid formation
2. Wound dehiscence (separation of wound edges)
3. Infection
4. Chronic non-healing wounds
Factors affecting wound healing:
1. Local factors:
2. Systemic factors:
Factors affecting wound healing:
1. Local factors:
* Infection
* Poor blood supply
* Foreign bodies
* Mechanical stress
2. Systemic factors:
* Age
* Nutrition
* Diabetes
* Medications (e.g., steroids)
* Smoking
* Obesity
* Stress
TLO 4.4 Describe the stages of wound healing
The stages of wound healing are:
- Hemostasis (immediate):
* Vasoconstriction
* Platelet aggregation
* Fibrin clot formation - Inflammatory phase (1-4 days):
* Neutrophil and macrophage infiltration
* Removal of debris and bacteria - Proliferative phase (4-21 days):
* Angiogenesis
* Fibroblast proliferation
* Collagen synthesis
* Granulation tissue formation
* Re-epithelialization - Remodeling phase (21 days to 1 year):
* Collagen reorganization
* Scar maturation
* Gradual regain of tissue strength
Topic 5 – Basics of Neoplasia
TLO 5.1 Define and classify neoplasms
A neoplasm is an abnormal mass of tissue resulting from uncontrolled, excessive growth of cells that persists even after the initial stimulus is removed.
Classification of neoplasms:
Classification of neoplasms:
1. By behavior:
* Benign
* Malignant (cancer)
* Potentially malignant (in situ)
2. By tissue of origin:
Carcinomas: Originate from epithelial tissue (e.g., skin, lining of organs)
Sarcomas: Originate from connective tissue (e.g., bone, muscle, cartilage)
Leukemias: Cancers of the blood-forming cells (white blood cells, red blood cells, platelets)
Lymphomas: Cancers of the lymphatic system (lymph nodes, spleen)
TLO 5.2 Discuss the features of benign neoplasms
Features of benign neoplasms:
- Slow growth rate
- Well-circumscribed and often encapsulated
- Resemblance to tissue of origin (well-differentiated)
- Lack of invasion into surrounding tissues
- No metastasis
- Limited effect on host (unless in a critical location)
- Generally good prognosis
- Often can be surgically removed with low risk of recurrence
TLO 5.3 Discuss the features of malignant neoplasms with examples
Features of malignant neoplasms:
Features of malignant neoplasms:
1. Rapid, uncontrolled growth
2. Poorly circumscribed and invasive
3. Loss of differentiation (anaplasia)
4. Invasion of surrounding tissues
5. Ability to metastasize
6. Significant effect on host health
7. Poor prognosis if untreated
8. High risk of recurrence after treatment
Examples:
* Carcinomas: Lung cancer, breast cancer, colorectal cancer
* Sarcomas: Osteosarcoma, leiomyosarcoma
* Hematologic malignancies: Leukemias, lymphomas
* Brain tumors: Glioblastoma multiforme
TLO 5.4 List the differences between benign and malignant neoplasms
Differences between benign and malignant neoplasms:
- Growth rate: Benign - slow; Malignant - rapid
- Differentiation: Benign - well-differentiated; Malignant - poorly differentiated
- Capsule: Benign - often encapsulated; Malignant - not encapsulated
- Invasion: Benign - no invasion; Malignant - invasive growth
- Metastasis: Benign - no metastasis; Malignant - can metastasize
- Prognosis: Benign - generally good; Malignant - often poor if untreated
- Effect on host: Benign - limited; Malignant - significant
- Recurrence: Benign - rare; Malignant - common
- Nuclear features: Benign - normal; Malignant - abnormal (pleomorphism, hyperchromatism)
- Mitotic activity: Benign - low; Malignant - high, often abnormal
Topic 6 – Molecular Basis of Cancer
TLO 6.1 List the risk factors of cancer with examples
Risk factors for cancer include:
- Genetic factors: Inherited mutations (e.g., BRCA1/2 in breast cancer)
- Age: Increased risk with advancing age
- Tobacco use: Lung, mouth, throat cancers
- Alcohol consumption: Liver, esophageal, breast cancers
- Chronic infections: HPV (cervical cancer), Hepatitis B/C (liver cancer)
- Environmental toxins: Asbestos (mesothelioma), UV radiation (skin cancer)
- Diet: High red meat consumption (colorectal cancer)
- Obesity: Increased risk for various cancers including breast and colon
- Lack of physical activity: Increased risk for colon and breast cancers
- Hormonal factors: Prolonged estrogen exposure (breast cancer)
- Immunosuppression: Increased risk of various cancers
- Occupational exposures: Certain chemicals, radiation
TLO 6.2 Discuss the mechanism of action of oncogenes, tumor suppressor genes and DNA repair genes with examples
Oncogenes:
- Mechanism: Gain-of-function mutations in proto-oncogenes lead to increased cell proliferation or survival
- Examples:
1. RAS: Constitutively active in many cancers, promoting cell growth and survival
2. MYC: Overexpressed in various cancers, enhancing cell proliferation
3. HER2/neu: Amplified in some breast cancers, leading to increased cell division
Tumor suppressor genes:
- Mechanism: Loss-of-function mutations result in uncontrolled cell growth
- Examples:
1. TP53: “Guardian of the genome,” regulates cell cycle and apoptosis
2. RB: Controls cell cycle progression
3. APC: Regulates cell adhesion and signal transduction in colon cells
DNA repair genes:
- Mechanism: Mutations lead to genomic instability and accumulation of mutations
- Examples:
1. BRCA1/2: Involved in double-strand break repair, mutations increase breast and ovarian cancer risk
2. MLH1/MSH2: Mismatch repair genes, mutations cause Lynch syndrome
3. XPA/XPC: Nucleotide excision repair genes, mutations cause xeroderma pigmentosum
TLO 6.3 Discuss angiogenesis and metastasis of malignant tumors
Angiogenesis:
- Definition: Formation of new blood vessels to supply the tumor
- Process:
1. Tumor cells release pro-angiogenic factors (e.g., VEGF)
2. Endothelial cells are activated and proliferate
3. New blood vessels form and grow towards the tumor - Importance: Essential for tumor growth beyond 1-2 mm and facilitates metastasis
- Therapeutic target: Anti-angiogenic drugs (e.g., bevacizumab) can inhibit tumor growth
Metastasis
- Definition: Spread of cancer cells from primary site to distant organs
- Steps in metastasis:
1. Local invasion: Cancer cells break through basement membrane
2. Intravasation: Cells enter blood or lymphatic vessels
3. Survival in circulation: Cells resist immune attack and mechanical stress
4. Extravasation: Cells exit vessels at distant sites
5. Colonization: Cells adapt and grow in new environment
- Factors influencing metastasis:
- Epithelial-mesenchymal transition (EMT)
- Matrix metalloproteinases (MMPs)
- Adhesion molecules
- Chemokines and their receptors
* Common metastatic sites: Lungs, liver, bones, brain
TLO 6.4 Classify carcinogens and describe the mechanism of action of chemical carcinogens
Classification of carcinogens:
- Chemical carcinogens
- Physical carcinogens (e.g., radiation, asbestos)
- Biological carcinogens (e.g., viruses)
Chemical carcinogens can be further classified as:
- Direct-acting carcinogens
- Indirect-acting carcinogens (procarcinogens)
Mechanism of action of chemical carcinogens:
Chemical carcinogenesis is a multi-step process involving initiation, promotion, and progression. Initiation involves the initial DNA damage caused by the carcinogen. Promotion stimulates the growth of initiated cells. Progression involves further genetic and epigenetic changes that lead to the development of a malignant tumor.
- Initiation:
* Carcinogen or its metabolite interacts with DNA
* Forms DNA adducts or causes mutations
* Examples: Alkylating agents, polycyclic aromatic hydrocarbons (PAHs)
- Initiation:
- Promotion:
* Stimulates proliferation of initiated cells
* Does not directly damage DNA
* Examples: Phorbol esters, phenobarbital - Progression:
* Accumulation of additional genetic changes
* Leads to increased growth and invasive potential
Mechanism of action of chemical carcinogens:
Specific mechanisms:
Specific mechanisms:
1. Direct DNA damage: Alkylating agents form DNA adducts
2. Metabolic activation: Procarcinogens (e.g., benzo[a]pyrene) are activated by cytochrome P450 enzymes
3. Generation of reactive oxygen species: Leads to oxidative DNA damage
4. Epigenetic changes: Altered DNA methylation or histone modifications
5. Interference with DNA repair: Some carcinogens inhibit DNA repair mechanisms
This is for informational purposes only. For medical advice or diagnosis, consult a professional.
Chemical carcinogens can cause cancer by damaging DNA, the genetic material within cells. Here’s a simplified explanation of their mechanisms of action:
- Direct DNA Damage:
Direct Interaction: Some chemicals can directly react with DNA, causing:
DNA strand breaks: These disrupt the integrity of the DNA molecule.
DNA cross-linking: Chemical bonds form between different parts of the DNA strand, hindering normal cell function.
Base modifications: Chemical groups can be added to or removed from DNA bases, altering their structure and function.
- Indirect DNA Damage:
Metabolic Activation: Many chemicals are not directly harmful but are converted into reactive metabolites within the body. This often happens in the liver through the action of enzymes called cytochrome P450.
Reactive Metabolites: These activated forms of the chemical can then react with DNA, causing damage.
Key Takeaways:
Chemical carcinogens damage DNA in various ways, leading to mutations that can contribute to cancer development.
Some chemicals directly damage DNA, while others require metabolic activation to become harmful.
These mechanisms disrupt the normal cell cycle and can lead to uncontrolled cell growth and division, the hallmark of cancer.
Examples of chemical carcinogens:
- Tobacco smoke components (e.g., nitrosamines, PAHs)
- Aflatoxin B1 (produced by Aspergillus fungi)
- Vinyl chloride (industrial chemical)
- Benzene (solvent and industrial chemical)
- Arsenic compounds (environmental contaminant)
Chemical carcinogens are substances that can cause cancer by damaging DNA, the genetic material within cells. Here are some examples:
Industrial Chemicals:
Aromatic amines: Found in dyes, rubber, and some pharmaceuticals.
Polycyclic aromatic hydrocarbons (PAHs): Present in tobacco smoke, coal tar, and grilled food.
Vinyl chloride: Used in the production of PVC plastics.
Asbestos: A mineral used in insulation and construction materials.
Formaldehyde: Used in building materials, preservatives, and disinfectants.
Environmental Pollutants:
Air pollution: Includes particulate matter, nitrogen oxides, and other pollutants from vehicle exhaust and industrial emissions.
Water pollution: Contaminated water can contain industrial chemicals, pesticides, and heavy metals.
Soil contamination: Industrial waste and agricultural runoff can contaminate soil with harmful chemicals.
Lifestyle Exposures:
Tobacco smoke: Contains numerous carcinogens, including nicotine, tar, and PAHs.
Alcohol consumption: Excessive alcohol consumption can increase the risk of certain cancers, such as liver cancer.
Dietary factors: Processed meats, excessive red meat consumption, and diets low in fruits and vegetables can increase cancer risk.
Medical Treatments:
Chemotherapy drugs: Some chemotherapy drugs can increase the risk of secondary cancers.
Radiation therapy: High doses of radiation can damage DNA and increase the risk of cancer.
A 65-year-old man is brought to the ER with complaints of chest pain radiating to the left arm. He isdiagnosed to have myocardial infarction due to a block in the left anterior descending artery. Arepresentative section from the myocardial infarct is shown in the image. The infarct shows which typeof necrosis?
a.
Fibrinoid necrosis
b.
Liquefactive necrosis
c.
Caseous necrosis
d.
Coagulative necrosis
e.
Gangrenous necrosis
Coagulative necrosis
Factors that inhibit wound healing include all the following EXCEPT
a.
Advanced age
b.
Smoking
c.
Vitamin C
d.
Presence of foreign body
e.
Immunosuppression
Vitamin C
All of the following are TRUE regarding apoptosis EXCEPT
a.
The apoptotic cell attracts inflammatory cells
b.
It is programmed cell death
c.
The nucleus of the cell undergoes pyknosis
d.
Apoptotic bodies are phagocytosed by macrophages
The apoptotic cell attracts inflammatory cells
A 45-year-old patient diagnosed to have acute appendicitis undergoes appendicectomy. Grossexamination of the appendix will show all of the following EXCEPT
a.
Exudate on the serosa
b.
Fibrosis of the wall
c.
Edema of the wall
d.
Congested blood vessels
Fibrosis of the wall
A pathologist notes fatty change in the liver biopsy of a patient with history of alcohol abuse. This finding is an example of
a.
Apoptosis
b.
Reversible injury
c.
Irreversible injury
Reversible injury
The most common etiologic agent of gas gangrene is
a.
Escherichia coli
b.
Staphylococcus aureus
c.
Streptococcus pyogenes
d.
Clostridium perfringens
Clostridium perfringens
A 25-year-old male presents to the ER with complaints of productive cough and progressivelyincreasing swelling in the neck for 3 months which has not subsided with multiple courses of antibiotics.He gives a history of low-grade fever, loss of appetite and weight loss. On examination, he has mattedlymph nodes in the right supraclavicular region. Laboratory investigations show elevated ESR and CRP.Sputum AFB, Quantiferon Tb Gold and PCR for tuberculosis is positive. Microscopic examination ofbiopsy from the lymph node is given below. The multinucleate cells shown by the arrow head arederived from the fusion of
a.
Lymphocytes
b.
Neutrophils
c.
Basophils
d.
Eosinophils
e.
Epithelioid cells
Epithelioid cells
A 45-year-old patient diagnosed to have acute appendicitis undergoes appendicectomy. Microscopicexamination of a section from the appendix will show predominantly which type of inflammatory cells?
a.
Lymphocytes
b.
Macrophages
c.
Plasma cells
d.
Neutrophils
Neutrophils
A 72-year-old male was diagnosed with diffuse atherosclerotic cerebrovascular disease (blockage ofblood vessels by atherosclerotic plaques). The brain parenchyma in this patient will show
a.
Hypertrophy
b.
Atrophy
c.
Hyperplasia
d.
Metaplasia
Atrophy
Chemotaxis refers to
a.
Increased random movement of WBC’s
b.
Migration of WBC’s between endothelial cells to the site of inflammation
c.
Unidirectional locomotion of WBC’s directed by chemoattractants
d.
Migration of WBC’s through the basement membrane
Unidirectional locomotion of WBC’s directed by chemoattractants
The multinucleate cell found in TB granuloma is known as
a.
Langhans giant cell
b.
Popcorn giant cell
c.
Langerhans giant cell
d.
Reed Sternberg giant cell
Langhans giant cell
The sequence of cellular events in acute inflammation is
a.
Margination, rolling, transmigration, firm adhesion, chemotaxis, phagocytosis
b.
Margination, rolling, firm adhesion, chemotaxis, transmigration, phagocytosis
c.
Margination, rolling, firm adhesion, transmigration, chemotaxis, phagocytosis
d.
Margination, firm adhesion, rolling, transmigration, chemotaxis, phagocytosis
Margination, rolling, firm adhesion, transmigration, chemotaxis, phagocytosis
A 58-year-old man who presents to the ER with complaints of heart burn and dysphagia undergoesesophagoscopy. Microscopic examination findings of the oesophageal biopsy given shows which typeof adaptive change in the lining epithelium?
a.
Dysplasia
b.
Neoplasia
c.
Anaplasia
d.
Metaplasia
e.
Hyperplasia
Metaplasia
Diapedesis refers to
a.
Migration of RBC’s through the basement membrane
b.
Migration of leukocytes through the vessel wall to the site of inflammation
c.
Aggregation of platelets at the site of injury
Migration of leukocytes through the vessel wall to the site of inflammation
A 36-year-old lady presents with a painful mass in the breast ten days after a fall. Examination of thebreast shows a hard lump. Microscopic examination of the excised lump will show
a.
Caseous necrosis
b.
Fibrinoid necrosis
c.
Coagulative necrosis
d.
Fat necrosis
e.
Liquefactive necrosis
Fat necrosis
Microscopic examination of section from the liver following embolism of the hepatic artery shows ghostcells and increased eosinophilia of hepatocytes. This is a characteristic microscopic feature of
a.
Caseous necrosis
b.
Liquefactive necrosis
c.
Gangrenous necrosis
d.
Fat necrosis
e.
Coagulative necrosis
Coagulative necrosis
The maximum tensile strength of the injured tissue reached on wound healing compared to the normaltissue is
a.
100%
b.
50%
c.
80%
d.
30%
80%
Non-caseating granulomas are seen in all the following EXCEPT
a.
Sarcoidosis
b.
Hodgkin lymphoma
c.
Crohn disease
d.
Tuberculosis
Tuberculosis
A 50-year-old man who presents to the ER with complaints of chest pain for one day is diagnosed tohave a myocardial infarct. He dies before intervention. Microscopic examination of the infarct will show
a.
Liquefactive necrosis of cardiac myocytes with lymphocyte infiltrate
b.
Caseous necrosis of cardiac myocytes with plasma cell infiltrate
c.
Coagulative necrosis of cardiac myocytes with neutrophil infiltrate
d.
Fibrinoid necrosis of cardiac myocytes with macrophage infiltrate
e.
Dense fibrous scar
Coagulative necrosis of cardiac myocytes with neutrophil infiltrate
Reversible Injury
Reversible Injury
Cells Undergo cloudy swelling
Cell Membrane Blebbing
Mitochondria Swollen and vacuolated
Nucleus Clumping of chromatin
Myelin Figures Rare
Endoplasmic Reticulum (ER) Swollen
Lysosomes Intact
Irreversible Injury
Irreversible Injury
Cells Cell death occurs
Cell Membrane Discontinuous
Mitochondria Amorphous density and calcification
Nucleus Pyknosis, karyorrhexis, karyolysis
Myelin Figures Swollen with loss of ribosomes
Endoplasmic Reticulum (ER) Swollen with loss of ribosomes
Lysosomes Ruptured with release of enzymes
Summary of Cellular Events
Cellular Events of Inflammation Caused/Mediated By
Margination Stasis of blood with reduced shear stress on endothelial cells
Rolling and Transient Adhesion Binding of selectins with their ligands
Firm Adhesion and Transmigration Binding of integrins (LFA-1 & VLA-4) to IgS CAMs (ICAM, VCAM, and JAM)
Binding of PECAM molecules
Chemotaxis Bacterial products, cytokines, components of the complement system, and phospholipids
Phagocytosis Interaction of TLRs (on phagocytes) with PAMPs (on the pathogen)
Mediators of Inflammation
Cell Derived Mediators Functions
Vasoactive Amines (Histamine, Serotonin) Vasodilation, increased vascular permeability, and smooth muscle contraction
Nitric Oxide (NO) Smooth muscle relaxation, vasodilation, inhibits platelet function
Cytokines Pro-inflammatory and anti-inflammatory action, functioning of the immune system, hematopoiesis, antiviral action, and acute phase response
Eicosanoids Vasodilation & increased vascular permeability (PGI2 and prostacyclin), vasoconstriction & platelet aggregation (thromboxane, leukotriene)
Reactive Oxygen Species Microbial killing, cell damage, and inflammatory response
Lysosomal Enzymes Increase vascular permeability, chemotaxis of inflammatory cells, activation of complement components, degrade bacteria and extracellular matrix
Platelet Activating Factor (PAF) Vasodilation, platelet activation, increased vascular permeability, and bronchoconstriction
Common Benign Tumors & Their Malignant Counterparts
Common Benign Tumors & Their Malignant Counterparts
Epithelial Tissue
Benign Tumor: Squamous cell papilloma
Malignant Tumor: Squamous cell carcinoma
Connective Tissue
Fibrocyte
Benign Tumor: Fibroma
Malignant Tumor: Fibrosarcoma
Cartilage
Benign Tumor: Chondroma
Malignant Tumor: Chondrosarcoma
Bone
Benign Tumor: Osteoma
Malignant Tumor: Osteosarcoma
Fat
Benign Tumor: Lipoma
Malignant Tumor: Liposarcoma
Bone Marrow
No benign tumor
Malignant Tumor: Leukemia
Lymph Node
Benign Tumor: Lymphoma
Malignant Tumor: Lymphosarcoma
Blood Vessel
Benign Tumor: Hemangioma
Malignant Tumor: Hemangiosarcoma
Muscle Tissue
Smooth Muscle
Benign Tumor: Leiomyoma
Malignant Tumor: Leiomyosarcoma
Skeletal Muscle
Benign Tumor: Rhabdomyoma
Malignant Tumor: Rhabdomyosarcoma
Retinoblastoma gene and TP53 gene mutations are examples of which mechanism that could lead to cancer?
Retinoblastoma gene and TP53 gene mutations are examples of which mechanism that could lead to cancer?
Increasing apoptosis
Proto-oncogenes being converted to oncogenes
Inactivation of tumor suppressor genes (selected)
Mutation in DNA repair genes
Match the neoplasm with its description
Match the neoplasm with its description
Squamous cell carcinoma:
Malignant tumor of epithelial cells
Chondroma:
Benign tumor of cartilage
Osteosarcoma:
Malignant tumor of bone
Leiomyoma:
Benign tumor of smooth muscle
Liposarcoma:
Malignant tumor of adipocytes
Which of the following can cause chronic inflammation? Select all that apply:
Persistent infection
Autoimmune disorder
Acute exposure to an environmental toxin
Chronic exposure to an environmental toxin
Which of the following can cause chronic inflammation? Select all that apply:
☑ Persistent infection
☑ Autoimmune disorder
☐ Acute exposure to an environmental toxin
☑ Chronic exposure to an environmental toxin
What is the convergence point of both the intrinsic and extrinsic pathways of apoptosis?
Executor caspases activated
Initiator caspases activated
Increased BAX and BAK proteins
Fas ligand binding to Fas receptor
Cytochrome c leakage from mitochondria
What is the convergence point of both the intrinsic and extrinsic pathways of apoptosis?
Initiator caspases activated
Match the cell adaptation to its description
Match the cell adaptation to its description
Hypertrophy: Increase in the size of cells
Atrophy: Decrease in the size of cells
Hyperplasia: Increase in the number of cells
Metaplasia: Change to a different cell type
TLO 1.1: Gametogenesis Comparison
Spermatogenesis:
Continuous in males from puberty.
Produces four functional spermatids from one primary spermatocyte.
Takes ~64 days to complete.
Results in small, motile gametes.
Spermatogenesis is the process of producing sperm cells in males. It happens in the testes and involves several steps:
1. Formation of Sperm Cells: It starts with spermatogonia (stem cells), which divide to form immature sperm cells.
2. Meiosis: These immature cells undergo meiosis, a type of cell division that reduces the chromosome number by half, creating four haploid sperm cells.
3. Maturation: The haploid cells mature into fully functional sperm, gaining a tail for swimming and a head containing genetic material.
Spermatogenesis ensures that sperm are ready for reproduction, carrying half the genetic information needed to form an offspring.
TLO 1.1: Gametogenesis Comparison
Oogenesis:
Oogenesis is the process of creating an egg, or ovum, in a female fetus. It starts in the ovaries around seven weeks into gestation.
Process
Primordial germ cells: In the female fetus, primordial germ cells (PGCs) colonize the ovaries.
Mitosis: PGCs undergo mitosis to become oogonia.
Oogonia become primary oocytes: Oogonia undergo maturation to become primary oocytes.
Meiosis: Primary oocytes undergo meiosis, which separates paired chromosomes and chromatids. This results in a secondary oocyte, which will complete meiosis if fertilized.
Ovulation: The secondary oocyte is released from the ovary during ovulation
TLO 1.2: Meiosis and Genetic Variability
Mechanisms for Variability:
Meiosis generates genetic variability primarily through two mechanisms:
crossing over (genetic recombination) which occurs during prophase I, and
independent assortment of chromosomes during metaphase I,
where homologous chromosomes randomly align, leading to diverse combinations of alleles in the resulting gametes
Independent assortment: Random alignment of chromosomes during metaphase I.
Crossing over: Exchange of genetic material during prophase I.
Random fertilization: Fusion of genetically diverse gametes.
TLO 1.2: Meiosis and Genetic Variability
Significance:
Promotes adaptation, disease resistance, and species evolution.
TLO 1.3: Fertilization and Zygotic Cleavage
Fertilization:
Fertilization is the process where a sperm cell penetrates an ovum (egg), essentially merging their genetic material to create a zygote, which marks the beginning of a new individual’s development; in simpler terms, it is when a sperm “penetrates the egg.
Sperm penetrates the ovum.
Pronuclei fuse to restore diploid chromosome number.
Cortical reaction prevents polyspermy.
Calcium triggers completion of meiosis II in the ovum.
TLO 1.3: Fertilization and Zygotic Cleavage
Zygotic Cleavage:
Zygotic cleavage is the process of cell division that occurs after fertilization to create a multicellular embryo. It is a series of mitotic divisions that produce smaller cells called blastomeres
Zygotic cleavage is the series of rapid cell divisions that occur after a zygote (fertilized egg) is formed. During this process:
1. Zygote to Blastomeres: The single-celled zygote divides into smaller cells called blastomeres without increasing in overall size.
2. No Growth Phase: The cleavage divisions lack a growth phase, meaning the total volume of the embryo remains the same while the cells become progressively smaller.
3. Formation of a Multicellular Structure: This process eventually forms a solid ball of cells (morula) or a hollow structure (blastula), depending on the organism.
Zygotic cleavage lays the foundation for the later stages of embryonic development by creating the cells that will differentiate into tissues and organs.
TLO 1.4: Blastogenesis and Endometrial Implantation
Blastogenesis:
“Blastogenesis” refers to the early stage of embryonic development where a fertilized egg (zygote) divides rapidly to form a blastocyst, characterized by the formation of a fluid-filled cavity called the blastocoel, with an inner cell mass (which will become the embryo) surrounded by an outer layer of cells called the trophoblast (which will develop into the placenta)
Morula compacts and forms a blastocoel.
Blastocyst develops (inner cell mass + trophoblast).
TLO 1.4: Blastogenesis and Endometrial Implantation
Implantation:
“Implantation” refers to the process where a blastocyst, a ball of cells developed from a fertilized egg, attaches to and burrows into the lining of the uterus (endometrium), marking the initial stage of pregnancy; essentially, it’s the moment the embryo becomes embedded in the uterine wall and starts to develop further.
Blastocyst hatches from the zona pellucida.
Trophoblast attaches to and invades the endometrium.
Syncytiotrophoblast completes implantation (day 11–12 post-fertilization).
TLO 1.4: Blastogenesis and Endometrial Implantation
Consequences of Failure:
Sign of failed implantation. Cramping and spotting after a failed implantation is your body expelling the embryo after it failed to attach to the uterine wall
When implantation does not occur, a timely destruction of the fully developed endometrium leads to menstruation.
Recurrent implantation failure (~10% in IVF).
Causes: Immunological, thrombophilias, or embryo aneuploidy.
TLO 1.5: Germ Layers and Tissue Formation
Ectoderm
Mesoderm
Endoderm
The three germ layers, ectoderm, mesoderm, and endoderm, are the primary cell layers that develop early in an embryo and give rise to all the different tissues and organs in the body; with the ectoderm forming the skin and nervous system, the mesoderm forming muscles, bones, and connective tissue, and the endoderm forming the lining of the digestive and respiratory systems.
Breakdown:
Ectoderm (Outer Layer):
Develops into the epidermis (outer layer of skin), hair, nails, brain, spinal cord, and neural tissue.
Mesoderm (Middle Layer):
Develops into skeletal muscles, bones, cartilage, blood vessels, kidneys, and the reproductive organs.
Endoderm (Inner Layer):
Develops into the lining of the digestive tract, lungs, liver, pancreas, and other internal organs associated with the digestive system.
Topic 2: Epithelial Tissue
TLO 2.1: Embryonic Origin
Originates from:
Ectoderm
Mesoderm
Endoderm
Serosal membranes
Ectoderm: Epidermis, sweat glands.
Mesoderm: Kidney tubules, gonads.
Endoderm: Gastrointestinal and respiratory tract lining.
Serosal membranes: Primarily mesodermal origin.
TLO 2.2: Serosal Membranes
Location:
Composition:
Function:
Examples:
TLO 2.2: Serosal Membranes
Location: Line cavities and cover organs.
Composition: Simple squamous epithelium + connective tissue.
Function:
Reduce friction.
Produce lubricating fluid.
Compartmentalize body cavities.
Examples: Pleura, pericardium, peritoneum.
Serous membranes line body cavities and cover organs in those cavities. They are made up of two layers of mesothelial cells and secrete a thin, watery fluid called serous fluid. Serous membranes reduce friction between organs and the walls of the body cavity.
Location Serous membranes line the following cavities:
Thoracic cavity: The pleura lines the thoracic cavity and covers the lungs
Abdominal cavity: The peritoneum lines the abdominal cavity and covers the abdominal organs
Pericardial cavity: The pericardium surrounds the heart
Vaginal cavity: The tunica vaginalis surrounds the testes in males
Composition Serous membranes are made up of two layers of mesothelial cells. The visceral layer covers the organ, while the parietal layer covers the cavity wall.
Function Serous membranes reduce friction between organs and the walls of the body cavity. They also provide structural support and act as a protective barrier.
TLO 2.3: Epithelial Tissue Types
Simple squamous
Simple cuboidal
Simple columnar
Stratified squamous
Stratified cuboidal
Stratified columnar
Pseudostratified columnar
TLO 2.3: Epithelial Tissue Types
Simple squamous: Lines blood vessels and body cavities, and regulates the passage of substances
Simple cuboidal: Found in kidney tubules and glandular tissue, and secretes and absorbs substances
Simple columnar: Lines the stomach and intestines, and absorbs and secretes substances
Stratified squamous: Protects the body from microorganisms and water loss, and is the main component of the skin
**Stratified cuboidal: **Found in the excretory ducts of sweat and salivary glands
**Stratified columnar: **Found in the conjunctiva of the eyelids, and protects and secretes mucus
**Pseudostratified columnar: **Found in the trachea and upper respiratory tract, and secretes mucus
Simple squamous: Diffusion/filtration (e.g., alveoli).
Simple cuboidal: Secretion/absorption (e.g., kidney tubules).
Simple columnar: Absorption/secretion (e.g., intestinal lining).
Stratified squamous: Protection (e.g., esophagus).
Stratified cuboidal: Protection/secretion (e.g., sweat glands).
Stratified columnar: Protection/secretion (e.g., male urethra).
Pseudostratified columnar: Secretion/cilia action (e.g., respiratory tract).
TLO 2.4: Histological Identification
Based on:
Cell shape
Layers
Specialized structures
TLO 2.4: Histological Identification
Based on:
Cell shape (squamous, cuboidal, columnar).
Layers (simple, stratified).
Specialized structures (cilia, microvilli).
Cell shape
Squamous: Flat shape, with a width greater than its height
Cuboidal: Cube shape, with a width and height that are roughly equal
Columnar: Column shape, with a width smaller than its height
Layers
Simple: One layer of cells
Stratified: Two or more layers of cells
Pseudostratified: Appears to be stratified, but is actually one layer of cells
TLO 2.5: Cell Junctions
Tight junctions
Adherens junctions
Desmosomes
Gap junctions
TLO 2.5: Cell Junctions
Tight junctions: Seal adjacent cells (e.g., blood-brain barrier).
Adherens junctions: Anchor cells (e.g., epithelial sheets).
Desmosomes: Strong adhesion (e.g., skin epidermis).
Gap junctions: Cell communication (e.g., cardiac muscle).
Tight junctions:
Create a watertight seal between cells, preventing leakage of fluids and molecules between them, essentially acting as a barrier function; often found in epithelial tissues like the lining of the bladder or stomach.
Adherens junctions:
Anchor cells to each other by connecting to the actin cytoskeleton, providing structural support and allowing for cell-to-cell adhesion; involved in cell migration and tissue development.
Desmosomes:
Strong, spot-like junctions that connect the intermediate filaments of neighboring cells, providing strong mechanical stability and resisting shearing forces; commonly found in tissues experiencing high stress like skin.
Gap junctions:
Form channels between cells allowing for direct communication and passage of small molecules like ions, enabling rapid electrical signaling between cells
TLO 2.6: Glandular Tissue
Exocrine glands:
Simple:
Compound:
Endocrine glands:
TLO 2.6: Glandular Tissue
Exocrine glands:
Simple: Single duct (e.g., sweat glands).
Compound: Branched ducts (e.g., salivary glands).
Endocrine glands:
Secrete directly into bloodstream (e.g., thyroid).
Exocrine glands secrete substances through ducts onto the body’s surfaces, while endocrine glands secrete substances directly into the bloodstream. The pancreas is an organ that contains both exocrine and endocrine glands.
Exocrine glands
Pancreas: Secretes digestive enzymes into the duodenum, such as trypsinogen and chymotrypsinogen. The pancreas also secretes bicarbonate ions to neutralize acidic chyme.
Sweat glands: Secrete sweat onto the body’s surface
Lacrimal glands: Secrete tears onto the body’s surface
Salivary glands: Secrete saliva onto the body’s surface
Mammary glands: Secrete milk onto the body’s surface
Endocrine glands
Pituitary gland: Located in the brain, this gland secretes hormones that regulate metabolism, mood, and sexual reproduction.
Thyroid gland: An endocrine gland that secretes hormones.
Adrenal glands: Located on top of each kidney, these glands secrete hormones that regulate metabolism, blood pressure, and the body’s stress response.
Pineal gland: Located at the base of the brain, this gland secretes melatonin, which helps regulate sleep and circadian rhythms.
Parathyroid glands: Located in the neck, these glands regulate calcium levels in the blood.
TLO 2.7: Exocrine Secretion Mechanisms
Merocrine:
Apocrine:
Holocrine:
TLO 2.7: Exocrine Secretion Mechanisms
Merocrine: Exocytosis (e.g., pancreatic enzymes).
Apocrine: Cytoplasm released with secretion (e.g., mammary glands).
Holocrine: Entire cell disintegrates (e.g., sebaceous glands).
The most damaging type of secretion to cells is holocrine, whereas merocrine is the least damaging, and apocrine is in between them. Note: -Endocrine glands are the glands that release their secretions directly into the blood and hence they are known as ductless glands.
Merocrine
The most common type of gland, merocrine glands release secretions through exocytosis. This process doesn’t damage the cell. Examples of merocrine glands include eccrine sweat glands, which are found in the palms of the hands and soles of the feet.
Apocrine
Apocrine glands release secretions by pinching off part of the cell membrane. This causes the cell to lose some of its cytoplasm. Examples of apocrine glands include mammary glands, which produce breast milk.
Holocrine
Holocrine glands release secretions by rupturing the cell membrane. This destroys the cell, causing the entire cell to become part of the secretion. Examples of holocrine glands include sebaceous glands, which produce sebum, an oily substance that lubricates the skin.
Topic 3: Connective Tissue
TLO 3.1: Embryonic Origin
Mesoderm:
Mesenchyme:
Hematopoietic stem cells:
Mesoderm: A layer of cells in the middle of an organism.
Mesenchyme: An embryonic connective tissue that comes from the mesoderm.
Hematopoietic stem cells: Cells that produce all the cells in the blood.
Mesoderm:
Mesenchyme: Fibroblasts, adipocytes.
Hematopoietic stem cells: Blood cells, immune cells.
TLO 3.2: Connective Tissue Cell Types
Fibroblasts:
Adipocytes:
Macrophages:
Mast cells:
Plasma cells:
Chondrocytes:
Osteoblasts/Osteocytes:
TLO 3.2: Connective Tissue Cell Types
Fibroblasts: ECM synthesis.
**Adipocytes: **Fat storage.
Macrophages: Phagocytosis.
**Mast cells: **Inflammatory mediators.
Plasma cells: Antibody production.
Chondrocytes: Cartilage matrix maintenance.
Osteoblasts/Osteocytes: Bone matrix maintenance.
1. Fibroblasts: These cells are essential for producing and maintaining the extracellular matrix, which provides structural support to tissues. They are especially involved in wound healing, creating collagen and other fibers.
**2. Adipocytes: **Also known as fat cells, adipocytes store energy in the form of fat. They play critical roles in metabolism, energy balance, and insulation. There are two types of adipocytes: white fat cells and brown fat cells.
**3. Macrophages: **These are key players in the immune system, responsible for detecting, engulfing, and destroying pathogens and dead cells. They also stimulate other immune cells and are involved in inflammation and tissue repair.
4. Mast Cells: Part of the immune system, mast cells play a pivotal role in* allergic reactions and inflammatory processes*. They release histamine and other chemicals during immune responses, contributing to inflammation.
5. Plasma Cells: These are mature B-lymphocytes that produce antibodies to fight against pathogens. They are an essential component of the adaptive immune system.
**6. Chondrocytes: **These cells are found in cartilage and are responsible for the synthesis and maintenance of cartilage matrix. They help maintain the structural integrity of cartilage tissue.
7. Osteoblasts/Osteocytes: Osteoblasts are cells that form new bone, synthesizing and secreting the bone matrix. Once they become embedded in the matrix they create, they differentiate into osteocytes. Osteocytes maintain bone tissue and are crucial for bone health and remodeling.
Topic 4: Skeletal Tissue
TLO 4.1: Bone Cell Types
Osteoblasts:
Osteocytes:
Osteoclasts:
Bone lining cells:
Topic 4: Skeletal Tissue
TLO 4.1: Bone Cell Types
Osteoblasts: Bone-forming cells; synthesize and secrete bone matrix.
Osteocytes: Mature bone cells; maintain bone tissue.
Osteoclasts: Bone-resorbing cells; break down bone matrix.
Bone lining cells: Inactive osteoblasts covering bone surfaces.
Osteoblasts Create new bone by secreting collagen and other proteins that bind to calcium and phosphate from the bloodstream.
Osteocytes Mature osteoblasts that maintain bone structure by regulating mineral concentration. They are the most common cell in bone and can live as long as the organism.
Osteoclasts Large cells that break down bone by dissolving minerals and collagen. They are found at the surface of bone where resorption is occurring.
Bone lining cells Protect bone surfaces from osteoclast activity when bone is not being remodeled. They also regulate the movement of minerals in and out of bone.
TLO 4.2: Bone Tissue Organization
Compact bone:
Spongy bone:
Periosteum:
Endosteum:
TLO 4.2: Bone Tissue Organization
Compact bone: Dense, organized with osteons (Haversian systems).
Spongy bone: Porous with trabeculae.
Periosteum: Outer fibrous layer covering bones.
Endosteum: Inner membrane lining bone cavities.
Compact bone
The dense, rigid outer layer of bone. It’s made up of osteons, which are microscopic units of calcified matrix.
Spongy bone
The lighter, less dense inner layer of bone. It’s made up of trabeculae and contains red bone marrow, which produces blood cells.
Periosteum
The tough, shiny membrane that covers the outer surface of most bones. It’s made of connective tissue and bone-forming cells, and helps bones grow, heal, and repair.
Endosteum
The delicate membrane that lines the cavities within bones, such as the medullary cavity.
TLO 4.3: Ossification Processes
Intramembranous ossification:
Intramembranous ossification is the process of creating bone tissue from connective tissue membranes. It’s a key part of fetal development and continues until a person is about 25 years old.
Intramembranous ossification: Intramembranous ossification: begins within fibrous connective tissue membranes formed by mesenchymal cells. Intramembranous ossification: Forms frontal, parietal, occipital, temporal, and clavicle bones.
Occurs in flat bones (e.g., skull, clavicle).
Mesenchymal cells differentiate directly into osteoblasts.
No cartilage intermediate.
TLO 4.3: Ossification Processes
Endochondral ossification:
Endochondral ossification is a process that replaces cartilage with bone during fetal development and bone growth. It’s one of the two main ways bone tissue is created in the mammalian skeletal system.
Occurs in long bones and vertebrae.
Cartilage model is replaced by bone.
Growth plates enable longitudinal growth.
TLO 4.3: Ossification Processes
Similarities:
Intramembranous and endochondral ossification are similar processes that both create bone tissue.
Similarities
Both processes produce bone tissue.
Both processes involve osteoblasts, which are cells that create bone.
Both processes occur before birth.
Differences
Intramembranous ossification: Forms bones from connective tissue, such as the skull.
Endochondral ossification: Forms bones from cartilage, such as long bones, short bones, and the ends of flat bones.
TLO 4.4: Common Bone Disorders
Osteoporosis:
Causes:
Osteomalacia/Rickets:
Causes:
Paget’s disease:
Causes:
Osteomyelitis:
Causes:
TLO 4.4: Common Bone Disorders
Osteoporosis
Bones become brittle and weak due to loss of bone density
Can be caused by aging, hormonal changes, and poor diet
Can be treated with medication or lifestyle changes
Rickets and osteomalacia
Bones become soft due to a lack of calcium or vitamin D
Can be caused by poor diet, lack of sunlight, or an inability to absorb vitamin D
Can be treated with vitamin supplements or a yearly vitamin D injection
Paget’s disease
Bones become misshapen due to excessive bone resorption and disorganized bone growth
Can affect the spine, pelvis, and skull
Can progress in the preexisting site, but does not spread to other bones
Other bone disorders include:
Osteogenesis imperfecta, which makes bones brittle
Renal osteodystrophy, which can be caused by kidney disease
Familial hypophosphatemia, a hereditary disorder that causes low levels of phosphate in the blood
Osteoporosis: Decreased bone density; increased fracture risk.
Causes: Age, hormonal changes, lack of exercise, poor nutrition.
Osteomalacia/Rickets: Inadequate mineralization.
Causes: Vitamin D deficiency, calcium or phosphate imbalance.
Paget’s disease: Abnormal remodelling.
Causes: Genetic factors, viral infections.
Osteomyelitis: Bone infection.
Causes: Bacterial/fungal infections via bloodstream or injury.
Topic 5: Blood
TLO 5.1: Major Components
Plasma:
Components:
Formed elements:
Includes:
The four main components of blood are plasma, red blood cells, white blood cells, and platelets.
Plasma
The liquid component of blood that carries blood cells throughout the body
Plasma is yellowish in color
Red blood cells
Also known as erythrocytes, these cells carry oxygen from the lungs to the body’s tissues
Red blood cells are the most common type of cell in blood
They are produced in bone marrow and have a diameter of about 6 micrometers
White blood cells
Also known as leukocytes, these cells help fight infections and disease
There are several types of white blood cells, including lymphocytes, monocytes, eosinophils, basophils, and neutrophils
Platelets
Also known as thrombocytes, these small, colorless cell fragments help stop bleeding
Platelets stick to the lining of blood vessels to help prevent or stop bleeding
Blood cells are produced in bone marrow, a spongy material in the center of bones.
Plasma: Liquid (55% of blood).
Components: Water, proteins, electrolytes, nutrients, hormones, waste.
Formed elements: Cellular (45% of blood).
Includes: Erythrocytes, leukocytes, platelets.
TLO 5.2: Blood Cell Types and Functions
Erythrocytes:
Leukocytes:
Neutrophils:
Lymphocytes:
Monocytes:
Eosinophils:
Basophils:
Platelets:
Erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets are all types of blood cells.
Erythrocytes
Also known as red blood cells (RBCs)
The most common type of blood cell
Carry oxygen from the lungs to the body’s tissues
Contain hemoglobin, a protein that carries oxygen
Leukocytes
Also known as white blood cells (WBCs)
Part of the immune system and help fight infection
Types of leukocytes include lymphocytes, monocytes, eosinophils, basophils, and neutrophils
Neutrophils
A type of white blood cell that helps heal damaged tissue and resolve infections
A lower than normal neutrophil count is called neutropenia
Lymphocytes
A type of white blood cell that helps the body make cells that fight infection and make antibodies
Part of the adaptive immune system
Monocytes
A type of white blood cell that helps other white blood cells remove damaged tissue and gobble up bacteria, viruses, debris, and infectious organisms
Eosinophils
A type of white blood cell that kills parasites, destroys cancer cells, and helps the immune system with an allergic response
Contain granules that contain antihistamine molecules and molecules toxic to parasitic worms
Basophils
A type of white blood cell that releases histamine if there is an allergic reaction and helps prevent blood clots
Platelets Also known as thrombocytes, Help in blood clotting, and A low number of platelets is called thrombocytopenia.
Erythrocytes: Oxygen transport; biconcave, no nucleus.
Leukocytes: Immune defense.
Neutrophils: Bacteria phagocytosis.
Lymphocytes: Adaptive immunity (T/B cells).
Monocytes: Phagocytosis, antigen presentation.
Eosinophils: Parasite defense, allergic response.
Basophils: Release inflammatory mediators.
Platelets: Blood clotting; derived from megakaryocytes.
TLO 5.3: Myeloid vs. Lymphoid Cell Lines
Myeloid:
Lymphoid:
TLO 5.3: Myeloid vs. Lymphoid Cell Lines
Myeloid cells give rise to various cells, including red blood cells, platelets, granulocytes (neutrophils, eosinophils, basophils), monocytes, and dendritic cells. Lymphoid cells produce lymphocytes, including B cells, T cells, and natural killer (NK)
Myeloid:
Includes: Erythrocytes, platelets, granulocytes, monocytes.
Shorter lifespan.
Lymphoid:
Includes: T/B lymphocytes, NK cells.
Primarily adaptive immunity.
TLO 5.4: Erythrocyte Dysfunction and Anemias
Iron deficiency anemia:
Vitamin B12 deficiency:
Sickle cell anemia:
Thalassemia:
Iron deficiency anemia, vitamin B12 deficiency, sickle cell anemia, and thalassemia are all types of anemia. Anemia is a blood disorder that occurs when your body doesn’t have enough healthy red blood cells.
**Iron deficiency anemia
**Occurs when your body doesn’t have enough iron to produce hemoglobin
Can be caused by poor diet or blood loss
Can be treated by eating iron-rich foods and foods rich in vitamin C
**Vitamin B12 deficiency anemia
**Occurs when your body doesn’t have enough vitamin B12
Can be caused by inadequate intake or absorption issues
Can be treated with vitamin B12 supplements, injections, or nose sprays
**Sickle cell anemia
**An inherited disease that can cause anemia
Thalassemia
An inherited disease that can cause anemia
Beta-thalassemia minor is often discovered during a routine blood count
**Other causes of anemia include:
**Folate deficiency, Chronic diseases, Infections, Certain medications, Bleeding, and Bone marrow problems.
**Symptoms of anemia include:
**Weakness
Dizziness
Shortness of breath
Headache
Pale or yellow skin
Chest pain
Iron deficiency anemia: Insufficient iron; microcytic, hypochromic.
Vitamin B12 deficiency: Impaired DNA synthesis; macrocytic, neurological symptoms.
Sickle cell anemia: Hemoglobin mutation; sickle-shaped cells, crises.
Thalassemia: Defects in globin chain production; microcytic anemia.
Topic 6: Muscular Tissue
TLO 6.1: Key Characteristics
Excitability
Contractility
Extensibility
Elasticity
Excitability:
When a muscle receives a signal from a nerve, it can respond by initiating a contraction.
Contractility:
This is the primary function of muscle tissue, where the muscle fibers shorten to generate force.
Extensibility:
Muscles can be stretched without tearing, allowing for flexibility in movement.
Elasticity:
After being stretched, a muscle can recoil back to its original length due to its elastic properties.
Excitability: Respond to stimuli.
Contractility: Shorten and generate force.
Extensibility: Stretch without damage.
Elasticity: Return to original length.
TLO 6.2: Muscle Cell Types
Smooth muscle:
Skeletal muscle:
Cardiac muscle:
TLO 6.2: Muscle Cell Types
Smooth muscle: Involuntary, non-striated (e.g., hollow organs, vessels).
Skeletal muscle: Voluntary, striated (e.g., attached to bones).
Cardiac muscle: Involuntary, striated (e.g., heart).
Smooth muscle:
Found in the walls of internal organs like the stomach, bladder, and blood vessels, responsible for involuntary movements like digestion and blood pressure regulation; appears smooth under a microscope due to lack of striations.
Skeletal muscle:
Attached to bones, responsible for voluntary movements like walking and lifting; appears striated under a microscope and is controlled by the somatic nervous system.
Cardiac muscle:
Located only in the heart, responsible for pumping blood throughout the body; appears striated like skeletal muscle, but is involuntary and controlled by the autonomic nervous system.
Key differences:
Control:
Smooth and cardiac muscles are involuntary, while skeletal muscle is voluntary.
Location:
Skeletal muscles are attached to bones, while smooth muscle is found in internal organs and cardiac muscle is only in the heart.
Appearance:
Both cardiac and skeletal muscle appear striated under a microscope, while smooth muscle does not.
TLO 6.3: Muscle Contraction (Sliding Filament Theory)
Sliding filament theory, a muscle fiber contracts when myosin filaments pull actin filaments closer together and thus shorten sarcomeres within a fiber. When all the sarcomeres in a muscle fiber shorten, the fiber contracts.
Calcium released from sarcoplasmic reticulum.
Calcium binds troponin; myosin binding sites exposed on actin.
Myosin binds actin (cross-bridge formation).
ATP hydrolysis powers the power stroke.
ATP binding causes myosin release.
Cycle continues until calcium is removed.
Topic 7: Nervous Tissue
TLO 7.1: Embryonic Origins
Neural tube:
Neural crest:
In embryonic development, the neural tube originates from the folding of the neural plate, a structure formed from the ectoderm, and eventually develops into the central nervous system (brain and spinal cord), while the neural crest arises from the borders of the neural plate, migrating away to form a diverse range of cell types including neurons of the peripheral nervous system, cartilage, bone, and pigment cells.
Key points about their origins:
Neural tube:
Forms from the neural plate which is a thickened region of the ectoderm.
Folds inwards to create a tube-like structure.
Eventually develops into the brain and spinal cord.
Neural crest:
Develops at the edges of the neural plate, between the neural plate and the non-neural ectoderm.
Cells “delaminate” from the neural tube and migrate extensively throughout the embryo.
Differentiates into a wide variety of cell types depending on their migration pathway.
Neural tube: Forms CNS (brain, spinal cord).
Neural crest: Forms PNS and some CNS components.
TLO 7.2: Cellular Components
Neurons:
Glial cells:
Astrocytes:
Oligodendrocytes:
Microglia:
Ependymal cells:
Schwann cells:
Neurons
Neurons are divided into four types: unipolar, bipolar, multipolar, and pseudounipolar.
Neurons require help from glial cells to form strong connections and eliminate obsolete connections.
Glial cells
Glial cells are the most abundant cells in the central nervous system.
Glial cells help maintain homeostasis and form myelin.
Glial cells are classified by their morphology, location, function, and molecular composition.
Types of glial cells
Oligodendrocytes: Form the myelin sheath around axons in the central nervous system
Schwann cells: Form the myelin sheath around axons in the peripheral nervous system
Astrocytes: Provide nutrients, structural support, and maintain the extracellular environment of neurons
Microglia: Scavenge pathogens and dead cells
Ependymal cells: Produce cerebrospinal fluid that cushions neurons
Satellite cells: Provide nutrients and structural support to neurons in the peripheral nervous system
Radial glia: Involved in neurogenesis and neural development
Neurons: Transmit signals.
Glial cells:
Astrocytes: Support neurons; maintain blood-brain barrier.
Oligodendrocytes: Myelinate CNS axons.
Microglia: Immune defense.
Ependymal cells: Line ventricles; produce cerebrospinal fluid.
Schwann cells: Myelinate PNS axons.
TLO 7.3: Neural Cell Structures
Soma
Dendrites
Axon
Myelin sheath
Nodes of Ranvier
Soma:
This is the central part of a neuron, containing the nucleus and other organelles, essentially the “brain” of the cell where most cellular processes occur.
Dendrites:
These are short, branching extensions that extend from the soma and receive incoming signals from other neurons, acting like the “antennae” of the neuron.
Axon:
A long, thin fiber that carries electrical impulses away from the cell body to other neurons, muscles, or glands.
Myelin sheath:
A fatty layer that wraps around the axon, acting as an insulator to speed up signal transmission by allowing for “saltatory conduction” where the signal jumps between gaps in the myelin.
Nodes of Ranvier:
These are the gaps in the myelin sheath where the axon membrane is exposed, allowing for the signal to be regenerated and rapidly jump along the axon.
Soma: Signal integration.
Dendrites: Receive signals.
Axon: Conducts action potentials.
Myelin sheath: Insulates axons; speeds conduction.
Nodes of Ranvier: Gaps in myelin; enable saltatory conduction.
TLO 7.4: Myelin in CNS vs. PNS
CNS central nervous system:
PNS peripheral nervous system:
TLO 7.4: Myelin in CNS vs. PNS
CNS: Myelinated by oligodendrocytes; limited regeneration.
PNS: Myelinated by Schwann cells; better regeneration.
CNS: Includes only the brain and spinal cord.
PNS: Contains all nerves that extend from the brain and spinal cord to the body’s extremities.
Topic 8: Anatomical Position, Planes, and Terminology
TLO 8.1: Anatomical Position
Topic 8: Anatomical Position, Planes, and Terminology
TLO 8.1: Anatomical Position
Upright, face forward, arms at sides, palms forward, feet together.
TLO 8.2: Clinical Importance
Topic 8: Anatomical Position, Planes, and Terminology
Standardizes descriptions.
Aids in diagnosis, surgical planning, and imaging.
Anatomical position
Anterior: Toward the front of the body
Posterior: Toward the back of the body
Proximal: Close to the attachment point or trunk
Distal: Away from the attachment point or trunk
Superficial: Close to the surface of the skin
Deep: Away from the surface of the skin
Anatomical planes
Coronal plane: Separates the front and back of the body
Sagittal plane: Separates the left and right sides of the body
Transverse plane: Separates the upper and lower halves of the body
Anatomical terminology
Abdominopelvic cavity: The largest cavity in the body, which contains the digestive organs, kidneys, and adrenal glands
Pelvic cavity: Contains the rectum and most of the urogenital system
Cranial: A term used to refer to the skull
Cephalic: A term used to refer to the skull
Rostral: A term used to refer to the front of the face
Caudal: A term used in embryology and occasionally in human anatomy
TLO 8.3: Anatomical Planes
Sagittal:
Coronal:
Transverse:
Sagittal: Left/right.
Coronal: Front/back.
Transverse: Top/bottom.
TLO 8.4: Terminology
Directional:
Regional:
Cavities:
Movements:
TLO 8.4: Terminology
Directional: Superior, inferior, anterior, posterior, medial, lateral, proximal, distal.
Regional: Cephalic, thoracic, abdominal, pelvic.
Cavities: Dorsal (brain/spinal cord), ventral (thoracic, abdominopelvic).
Movements: Flexion, extension, abduction, adduction, rotation, pronation, supination.
Directional terms
Superior: Toward the head, or upper
Inferior: Away from the head, or lower
Anterior: Front
Posterior: Back
Medial: Toward the midline of the body
Lateral: Away from the midline of the body
Proximal: Closer to the trunk or point of attachment
Distal: Farther from the trunk or point of attachment
Superficial: Closer to the surface of the body
Deep: Farther from the surface of the body
Regional terms
The abdominopelvic cavity can be divided into regions or quadrants to describe the location of pain or masses
Cavities
Dorsal cavity
The cavity in the back of the body that contains the cranial and vertebral cavities
Ventral cavity
The cavity in the front of the body that contains the thoracic and abdominopelvic cavities
Thoracic cavity
The cavity within the rib cage that contains the heart and lungs
Abdominopelvic cavity
The largest cavity in the body that contains the digestive and reproductive organs
Topic 1: The Genetic Code and Mutations
TLO 1.1: Explain the central dogma of genetics
The central dogma of genetics outlines the flow of genetic information in living organisms:
The central dogma is summarized as:
DNA → RNA → Protein.
Topic 1: The Genetic Code and Mutations
Replication:
DNA is duplicated to ensure genetic material is inherited by daughter cells during cell division.
Topic 1: The Genetic Code and Mutations
Transcription:
DNA is transcribed into RNA (specifically, mRNA) by RNA polymerase.
Topic 1: The Genetic Code and Mutations
Transcription occurs in the nucleus and involves:
Promoters:
Exons:
Introns:
Promoters: Regions of DNA that signal RNA polymerase to start transcription.
Exons and introns: Exons are coding regions of mRNA; introns are spliced out.
Topic 1: The Genetic Code and Mutations
Translation:
mRNA is translated into proteins at the ribosome.
- Translation: mRNA is translated into proteins at the ribosome. This process involves:
tRNA:
Ribosomes:
Codons:
tRNA: Delivers amino acids.
Ribosomes: Facilitate peptide bond formation between amino acids.
Codons: Groups of three nucleotides in mRNA that encode specific amino acids.
TLO 1.2: Describe the genetic code and codons
Genetic Code:
A set of rules dictating how nucleotide sequences in mRNA are translated into proteins.
TLO 1.2: Describe the genetic code and codons
Codons:
Triplet nucleotide sequences (e.g., AUG) that code for amino acids or regulatory signals.
TLO 1.2: Describe the genetic code and codons
- Start codon:
- Stop codons:
- Start codon: AUG (methionine) initiates protein translation.
- Stop codons: UAA, UAG, UGA terminate translation.
TLO 1.2: Describe the genetic code and codons
Universal:
Degenerate:
Non-overlapping: .
TLO 1.2: Describe the genetic code and codons
Key Features:
* Universal: Shared by almost all organisms.
* Degenerate: Multiple codons can encode the same amino acid (e.g., UUU and UUC both encode phenylalanine).
* Non-overlapping: Each nucleotide is part of only one codon.
The genetic code is universal because all species use the same four bases A,T,C and G, and each base sequence codes for the same amino acid in all species. despite the 64 possible codons (sequence of three bases), there are only 20 possible amino acids. This means that multiple codons code for one amino acid, meaning the code is degenerate. Overlapping refers to how the code is read. The first three bases are read as one codon, then the next three as the second etc, therefore each base is read only once and the bases do not overlap.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Mutation:
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Mutation: A permanent change in the DNA sequence that can affect protein function.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Point mutations:
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Point mutations: A single nucleotide substitution.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Silent mutation:
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Silent mutation: No change in the encoded amino acid (e.g., CUU → CUC, both encode leucine).
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Missense mutation:
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Missense mutation: Changes the amino acid (e.g., Glu → Val in sickle cell anemia).
A missense mutation is a DNA change that results in different amino acids being encoded at a particular position in the resulting protein. Some missense mutations alter the function of the resulting protein.
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Nonsense mutation:
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Nonsense mutation: Converts a codon into a stop codon (e.g., UGC → UGA).
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Frameshift mutations:
TLO 1.3: Define mutations and differentiate between point vs. frameshift mutations
Frameshift mutations: Caused by insertion or deletion of nucleotides not in multiples of three, disrupting the reading frame.
Example: Adding one nucleotide to AUG-CUU becomes AUC-UUC, altering all downstream amino acids.
TLO 1.4: Describe trinucleotide repeat disorders
Examples:
TLO 1.4: Describe trinucleotide repeat disorders
Disorders caused by the abnormal expansion of three-nucleotide sequences within or near genes.
Normal individuals have stable numbers of repeats, but expanded repeats cause disease.
Examples:
Huntington’s disease: CAG repeats in the HTT gene cause toxic proteins.
Fragile X syndrome: CGG repeats in the FMR1 gene lead to gene silencing.
Myotonic dystrophy: CTG repeats in the DMPK gene interfere with protein interactions.
TLO 1.5: Define anticipation with disease examples
Anticipation:
A phenomenon where a genetic disorder worsens or manifests earlier in subsequent generations due to repeat expansions.
Examples:
Huntington’s disease: Earlier onset with paternal inheritance.
Myotonic dystrophy: Severity increases with maternal transmission.
Topic 2: Single Gene Disorders
Gene:
Topic 2: Single Gene Disorders
Gene: A DNA sequence encoding a protein or functional RNA.
Topic 2: Single Gene Disorders
Locus:
Topic 2: Single Gene Disorders
Locus: A gene’s location on a chromosome.
Topic 2: Single Gene Disorders
Allele:
Topic 2: Single Gene Disorders
Allele: Variant forms of a gene.
Topic 2: Single Gene Disorders
Genotype:
Topic 2: Single Gene Disorders
Genotype: The genetic makeup of an individual.
Topic 2: Single Gene Disorders
Phenotype:
Topic 2: Single Gene Disorders
Phenotype: Observable traits resulting from genotype-environment interactions.
Topic 2: Single Gene Disorders
Homozygous:
Topic 2: Single Gene Disorders
Homozygous: Possessing two identical alleles (e.g., AA or aa).
Topic 2: Single Gene Disorders
Heterozygous:
Topic 2: Single Gene Disorders
Heterozygous: Possessing two different alleles (e.g., Aa).
Topic 2: Single Gene Disorders
Dominant:
Topic 2: Single Gene Disorders
Dominant: A trait expressed with one allele (e.g., Aa or AA).
Topic 2: Single Gene Disorders
Recessive:
Topic 2: Single Gene Disorders
Recessive: A trait expressed only with two identical alleles (e.g., aa).
TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance
Autosomal dominant:
Examples:
Recurrence risk: 50% if one parent is affected.
TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance
Autosomal dominant: Requires only one mutated allele for the phenotype.
Examples: Marfan syndrome, Huntington’s disease.
Recurrence risk: 50% if one parent is affected.
TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance
Autosomal recessive:
Examples:
Recurrence risk:
TLO 2.2: Autosomal dominant inheritance vs. autosomal recessive inheritance
Autosomal recessive:
Requires two mutated alleles for the phenotype.
Examples: Cystic fibrosis, sickle cell anemia.
Recurrence risk: 25% if both parents are carriers.
TLO 2.3: X-linked inheritance
X-linked dominant:
Examples: .
TLO 2.3: X-linked inheritance
X-linked dominant:
Affects males and females.
Examples: Rett syndrome, hypophosphatemic rickets.
TLO 2.3: X-linked inheritance
X-linked recessive:
Examples:
Recurrence risk:
TLO 2.3: X-linked inheritance
X-linked recessive:
Affects males more severely; females are carriers.
Examples: Hemophilia A, Duchenne muscular dystrophy.
Recurrence risk: Sons of carrier mothers have a 50% chance of being affected.
TLO 2.4: Properties of mitochondrial inheritance
Examples:
TLO 2.4: Properties of mitochondrial inheritance
Inherited exclusively from the mother.
Affects tissues requiring high energy (e.g., brain, muscles).
Examples: Leber hereditary optic neuropathy (LHON), MELAS syndrome.
TLO 2.5: Define incomplete penetrance and pleiotropy
Incomplete penetrance:
Pleiotropy:
TLO 2.5: Define incomplete penetrance and pleiotropy
Incomplete penetrance: Not all individuals with a mutation exhibit symptoms (e.g., BRCA1 mutation carriers).
Pleiotropy: A single gene mutation impacts multiple systems (e.g., Marfan syndrome affects connective tissue, heart, and eyes).
TLO 2.6: Describe genetic imprinting and uniparental disomy
Genetic imprinting:
Uniparental disomy:
Examples:
Prader-Willi syndrome:
Angelman syndrome:
TLO 2.6: Describe genetic imprinting and uniparental disomy
Genetic imprinting: Differential expression of genes depending on their parental origin.
Uniparental disomy: Both chromosomes come from one parent.
Examples:
Prader-Willi syndrome: Paternal deletion on chromosome 15 or maternal uniparental disomy.
Angelman syndrome: Maternal deletion on chromosome 15 or paternal uniparental disomy.
Topic 3: Population Genetics
TLO 3.1: Define and Calculate Genotype Frequency and Allele
Frequency
Genotype Frequency
Genotype frequency refers to the proportion of individuals in a population with a specific genotype (e.g., homozygous dominant, heterozygous, or homozygous recessive). It is expressed as a fraction or percentage of the total population.
Mathematically:
f(Genotype)=Number of individuals with a specific genotypeTotal number of individuals in the populationf(Genotype)=Total number of individuals in the populationNumber of individuals with a specific genotype
Topic 3: Population Genetics
TLO 3.1: Define and Calculate Genotype Frequency and Allele
Allele Frequency
Allele Frequency
Allele frequency is the proportion of a specific allele (e.g., dominant or recessive) among all alleles at a particular locus in the population. Allele frequency is important because it measures genetic diversity within a population.
For a population with two alleles (A and a):
f(A)=2(AA)+(Aa)2N,f(a)=2(aa)+(Aa)2Nf(A)=2N2(AA)+(Aa),f(a)=2N2(aa)+(Aa)
Where:
* NN is the total number of individuals in the population.
Topic 3: Population Genetics
TLO 3.1: Define and Calculate Genotype Frequency and Allele
Example Calculation:
Suppose a population consists of 100 individuals with the following genotypes: 25 AAAA, 50 AaAa, and 25 aaaa.
Genotype frequencies:
f(AA)=25100=0.25,f(Aa)=50100=0.50,f(aa)=25100=0.25f(AA)=10025=0.25,f(Aa)=10050=0.50,f(aa)=10025=0.25
Allele frequencies:
f(A)=2(25)+50200=0.5,f(a)=2(25)+50200=0.5f(A)=2002(25)+50=0.5,f(a)=2002(25)+50=0.5
TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication
Definition of Hardy-Weinberg Equilibrium (HWE)
The Hardy-Weinberg equilibrium describes a theoretical state in which the allele and genotype frequencies in a population remain constant from generation to generation, provided certain assumptions are met.
TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication
Key Assumptions of HWE:
Key Assumptions of HWE:
- Large population size: Prevents genetic drift.
- No mutation: No new alleles are introduced or altered.
- Random mating: No preference for specific genotypes in mating.
- No natural selection: All genotypes have equal reproductive success.
- No gene flow: No migration into or out of the population.
TLO 3.2: Describe the Hardy-Weinberg Equilibrium and Its Implication
Implications:
The Hardy-Weinberg principle provides a baseline for measuring genetic variation and helps identify when evolutionary forces are acting on a population. If the observed genotype frequencies deviate from expected frequencies under HWE, one or more of the assumptions may be violated, indicating evolutionary change.
Mathematically, the equilibrium condition for a single gene with two alleles (A and a) is:
p2+2pq+q2=1p2+2pq+q2=1
Where:
- pp is the frequency of allele AA, and qq is the frequency of allele aa.
- p2p2: Frequency of homozygous dominant genotype (AAAA).
- 2pq2pq: Frequency of heterozygous genotype (AaAa).
- q2q2: Frequency of homozygous recessive genotype (aaaa).
TLO 3.3: Apply the Hardy-Weinberg Equilibrium to Calculate Genotype Frequency Estimates Application
Given allele frequencies (pp and qq), genotype frequencies can be estimated using the HWE equation.
Example:
In a population, the frequency of allele AA (pp) is 0.6, and the frequency of allele aa (qq) is 0.4 (p+q=1p+q=1).
Homozygous dominant (AAAA):
f(AA)=p2=(0.6)2=0.36f(AA)=p2=(0.6)2=0.36
Heterozygous (AaAa):
f(Aa)=2pq=2(0.6)(0.4)=0.48f(Aa)=2pq=2(0.6)(0.4)=0.48
Homozygous recessive (aaaa):
f(aa)=q2=(0.4)2=0.16f(aa)=q2=(0.4)2=0.16
These frequencies can be compared to observed data to determine if the population is in HWE.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Mutation:
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Mutation
Spontaneous changes in the DNA sequence introduce new alleles.
Mutations are the ultimate source of all genetic variation and are critical for evolution.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Genetic Recombination
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Genetic Recombination
During meiosis, homologous chromosomes exchange genetic material (crossing over), creating new allele combinations.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Gene Flow (Migration)
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Gene Flow (Migration)
Movement of individuals or gametes between populations introduces new alleles, increasing genetic diversity.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Genetic Drift
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Genetic Drift
Random changes in allele frequencies, especially in small populations, can lead to loss of genetic variation.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Natural Selection
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Natural Selection
Differential survival and reproduction of individuals with specific genotypes can increase or decrease genetic variation, depending on selective pressures.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Non-Random Mating
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Non-Random Mating
Assortative mating or inbreeding affects genotype frequencies and reduces heterozygosity.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Population Size
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Population Size
Larger populations tend to maintain more genetic variation due to reduced effects of genetic drift.
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Environmental Factors
TLO 3.4: Describe the Factors Responsible for Genetic Variation in Populations
Genetic Variation refers to the diversity of alleles and genotypes within a population. Several factors contribute to genetic variation:
Environmental Factors
Selective pressures, such as climate, predators, or food availability, influence which genotypes are advantageous.
Topic 4: Cytogenetics (Chromosomal Abnormalities)
TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature
Karyotype:
Topic 4: Cytogenetics (Chromosomal Abnormalities)
TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature
Karyotype: A display of an individual’s complete set of chromosomes arranged in pairs and sorted by size, centromere position, and banding pattern.
Chromosomes are visualized using stains (e.g., Giemsa stain for G-banding).
A normal karyotype includes 22 pairs of autosomes and 1 pair of sex chromosomes.
Topic 4: Cytogenetics (Chromosomal Abnormalities)
TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature
Chromosome nomenclature:
Example:
Topic 4: Cytogenetics (Chromosomal Abnormalities)
TLO 4.1: Demonstrate understanding of karyotypes and chromosome nomenclature
Chromosome nomenclature:
The total chromosome number, sex chromosomes, and any abnormalities are noted.
Example:
46,XX: Normal female.
47,XX,+21: Female with trisomy 21 (Down syndrome).
46,XY,t(9;22): Male with translocation between chromosomes 9 and 22 (Philadelphia chromosome, associated with chronic myeloid leukemia).
TLO 4.2: Discuss numerical chromosomal abnormalities
Numerical abnormalities:
Euploidy:
Aneuploidy:
TLO 4.2: Discuss numerical chromosomal abnormalities
Numerical abnormalities: Variations in chromosome number due to errors in cell division (nondisjunction or anaphase lag).
Euploidy: A normal set of chromosomes (e.g., 46 in humans).
Aneuploidy: Gain or loss of chromosomes.
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of autosomal aneuploidies:
Trisomy 21 (Down syndrome):
Trisomy 18 (Edwards syndrome):
Trisomy 13 (Patau syndrome):
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of autosomal aneuploidies:
Trisomy 21 (Down syndrome):
* Three copies of chromosome 21.
* Clinical features: Intellectual disability, hypotonia, characteristic facial features, congenital heart defects.
Trisomy 18 (Edwards syndrome):
* Three copies of chromosome 18.
* Clinical features: Severe developmental delays, overlapping fingers, rocker-bottom feet.
Trisomy 13 (Patau syndrome):
* Three copies of chromosome 13.
* Clinical features: Microcephaly, cleft lip/palate, polydactyly, congenital heart defects.
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of sex chromosome aneuploidies:
Turner syndrome (45,X):
Clinical features:
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of sex chromosome aneuploidies:
Turner syndrome (45,X):
Monosomy of the X chromosome in females.
Clinical features: Short stature, gonadal dysgenesis, webbed neck.
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of sex chromosome aneuploidies:
Klinefelter syndrome (47,XXY):
Clinical features:
TLO 4.2: Discuss numerical chromosomal abnormalities
Examples of sex chromosome aneuploidies:
Klinefelter syndrome (47,XXY):
Extra X chromosome in males.
Clinical features: Tall stature, hypogonadism, gynecomastia, infertility.
TLO 4.3: Describe the most common cause of numerical chromosomal abnormalities
Cause:
Nondisjunction:
TLO 4.3: Describe the most common cause of numerical chromosomal abnormalities
Cause: Most numerical abnormalities result from nondisjunction during meiosis.
Nondisjunction: Failure of homologous chromosomes (meiosis I) or sister chromatids (meiosis II) to separate.
This results in gametes with an extra or missing chromosome, leading to aneuploidy after fertilization.
TLO 4.4: Describe structural chromosomal abnormalities
Structural abnormalities:
Translocation:
Robertsonian translocation:
Deletion:
Inversion:
Paracentric inversion:
Pericentric inversion:
Ring chromosome:
Example:
TLO 4.4: Describe structural chromosomal abnormalities
Structural abnormalities: Result from chromosomal breakage and improper repair.
Translocation:
Exchange of segments between non-homologous chromosomes.
Robertsonian translocation: Fusion of two acrocentric chromosomes (e.g., t(14;21) associated with hereditary Down syndrome).
Deletion:
Loss of a chromosome segment.
Example: Cri-du-chat syndrome (5p deletion).
Inversion:
A chromosome segment is reversed end-to-end.
Paracentric inversion: Does not involve the centromere.
Pericentric inversion: Includes the centromere.
Ring chromosome: A circular chromosome formed when the ends fuse after breakage.
Example: Turner syndrome (ring X chromosome).
Topic 5: Genetics of Common Diseases
TLO 5.1: Discuss multifactorial inheritance and its influential factors
Multifactorial inheritance:
Examples of multifactorial diseases:
Type 2 diabetes:
Hypertension:
Congenital diseases:
Topic 5: Genetics of Common Diseases
TLO 5.1: Discuss multifactorial inheritance and its influential factors
Multifactorial inheritance: Results from the combined effect of multiple genes (polygenic) and environmental factors.
Examples of multifactorial diseases:
Type 2 diabetes: Influenced by genetic predisposition and lifestyle factors (e.g., obesity, diet).
Hypertension: Genetic susceptibility combined with environmental triggers (e.g., salt intake, stress).
Congenital diseases: Cleft lip/palate, neural tube defects (e.g., spina bifida).
TLO 5.2: Describe the multifactorial threshold model
Threshold model:
Example:
TLO 5.2: Describe the multifactorial threshold model
Threshold model: Explains the likelihood of developing a multifactorial disease.
Disease occurs when the combined genetic and environmental factors surpass a certain threshold.
The threshold varies between sexes and populations.
Example: Pyloric stenosis occurs more frequently in males, indicating a lower threshold for expression.
TLO 5.3: Discuss the assessment of recurrence risk for multifactorial diseases
Recurrence risk depends on:
Example:
TLO 5.3: Discuss the assessment of recurrence risk for multifactorial diseases
Recurrence risk depends on:
Number of affected relatives.
Severity of the condition in the proband.
Closeness of the familial relationship.
Population prevalence.
Example: Risk of neural tube defects decreases with folic acid supplementation but increases with maternal history of the defect.
Topic 6: Genetic Analysis
TLO 6.1: Describe genetic analysis and different methods used
Cytogenetic techniques:
Molecular techniques:
Biochemical analysis:
Topic 6: Genetic Analysis
TLO 6.1: Describe genetic analysis and different methods used
Genetic analysis involves studying DNA, RNA, and protein to identify mutations and chromosomal abnormalities.
Cytogenetic techniques: Karyotyping, fluorescence in situ hybridization (FISH).
Molecular techniques: PCR, next-generation sequencing (NGS), microarrays.
Biochemical analysis: Enzyme assays to detect metabolic abnormalities.
TLO 6.2: Describe different blotting techniques and their implications in diagnosis
Southern blot:
Northern blot:
Western blot:
TLO 6.2: Describe different blotting techniques and their implications in diagnosis
Southern blot:
Detects specific DNA sequences.
Used for large gene rearrangements (e.g., Duchenne muscular dystrophy).
Northern blot:
Analyzes RNA to study gene expression.
Example: Detection of gene silencing in Fragile X syndrome.
Western blot:
Detects specific proteins.
Example: Diagnosing HIV through detection of viral proteins.
TLO 6.3: Describe the polymerase chain reaction (PCR) and its use in genetic analysis
TLO 6.3: Describe the polymerase chain reaction (PCR) and its use in genetic analysis
PCR amplifies specific DNA sequences using primers and a thermostable DNA polymerase (e.g., Taq polymerase).
Steps:
Denaturation: DNA strands separate at high temperature.
Annealing: Primers bind complementary sequences.
Extension: DNA polymerase synthesizes the target sequence.
Applications: Detecting mutations (e.g., BRCA1/2 mutations in breast cancer). Pathogen detection (e.g., HIV, SARS-CoV-2).
TLO 6.4: Discuss different genetic diseases routinely screened in fetuses and newborns
Prenatal screening:
TLO 6.4: Discuss different genetic diseases routinely screened in fetuses and newborns
Prenatal screening:
Non-invasive tests:
Ultrasound for structural abnormalities.
Cell-free DNA (cfDNA) for detecting trisomies (e.g., trisomy 21, 18, 13).
Invasive tests:
Amniocentesis: Analyzes fetal karyotype.
Chorionic villus sampling (CVS): Detects genetic disorders.
Sickle cell anemia is caused by a missense mutation resulting in defective formation of a globin protein.In this condition, Glutamic acid is replaced by which of the following amino acids?
a.Phenylalanine
b.Proline
c.Arginine
d.Valine
e.Lysine
Sickle cell anemia is a condition due to missense mutation where Glutamic acid is replaced by Valine.Hydrophilic amino acid is replaced by hydrophobic amino acid in the outer surface of protein resultingin abnormal hemoglobin. It is an autosomal recessive disease caused by a point mutation in thehemoglobin beta gene (HBB) found on chromosome 11p15.5. Carrier frequency of HBB variessignificantly around the world, with high rates associated with zones of high malaria incidence, sincecarriers are somewhat protected against malaria. About 8% of the African American population arecarriers. A mutation in HBB results in the production of a structurally abnormal hemoglobin (Hb), calledHbS. Hb is an oxygen carrying protein that gives red blood cells (RBC) their characteristic color. Undercertain conditions, like low oxygen levels or high hemoglobin concentrations, in individuals who arehomozygous for HbS, the abnormal HbS clusters together, distorting the RBCs into sickled shapes.These deformed and rigid RBCs become trapped within small blood vessels and block them, producingpain and eventually damaging organs.
The correct answer is:
Valine
A man who is affected with hemophilia A (X-linked recessive) mates with a woman who is aheterozygous carrier of this disorder. What proportion of this couple’s daughters will be affected, and what proportion of the daughters will be heterozygous carriers?
a.0%; 100%
**b.50%; 50% **
c.100%; 0%
d.0%; 50%
e.2/3; 1/3
Because the man transmits his X chromosome to all of his daughters, all of the daughters must carry atleast one copy of the mutation. The mother will transmit a mutation-carrying X chromosome half thetime and a normal X chromosome half the time. Thus, half of the daughters will be heterozygouscarriers, and half will be affected homozygotes, having received a mutation from both parents.
The correct answer is:
50%; 50%
A woman who has a heterozygous genotype for the gene variant causing Phenylketonuria (PKU), mateswith an unrelated man homozygous for the normal gene variant. What is the risk that their child willhave PKU?
a.0%
b.100%
c.50%
d.25%
Which of the following terms is used to describe a disease that, from generation to generation, shows adecrease in the age of onset and an increase in the severity of symptoms?
a.Acceptation
b.Mutation
**c.Anticipation **
d.Assumption
Look at the pedigree below. If the male shown by the arrow in the fourth generation was to mate with ahomozygous normal female, what is the risk of their child also having the disease?
a.25%
b.75%
c.0%
d.100%
e.50%
In these situations, try to identify the pattern of inheritance first. The pattern shown here is autosomalrecessive because we can see that in generation I, the male parent is affected, whereas the femaleparent is normal. In the progeny, the sons and daughters are affected with an approximately equalfrequency. This shows it to be an autosomal trait.
It is not an X-linked trait, because the father contributes the X chromosome only to the daughter, not tothe son. Similarly, the Y chromosome is passed down to the son, not the daughter. Since the affectedfather has affected both the son and daughter, it is not a sex-linked trait, rather it is an autosomal trait.
Had it been a dominant trait, all the progeny would have been affected. Here we can see that ingeneration II, a son is normal. Also, in the next generation we can see the trait skipping a generation.This happens in case of a recessive trait. Recessive traits require two identical alleles for their expression.An affected child can have unaffected parents.
Hence, we can conclude that the given pedigree represents the transmission of an autosomal recessivetrait.
Now draw the punnett square based on what the question is asking.
Here the male is affected so in AR for them to be affected they should be homozygous for the disease;you can give any nomenclature to the allele but remember what nomenclature or color you are givinghere I will give ‘a’ for affected and ‘A’ for unaffected allele. So, the male’s genotype is aa. Now for thefemale it says homozygous and normal so her genotype is AA. If the question had said heterozygousnormal/carrier then it would have been Aa. But let’s go back to our scenario and draw a Punnett square.
a (male)
a (male)
A (female)
Aa
Aa
A (female)
Aa
Aa
As it is AR we need both affected allele’s to be inherited for the disease to be phenotypically visible orfor the individual to be affected. Hence the affected individual recurrence risk ratio is 0/4= 0%
But the risk of the child being a carrier for the disease is 4/4= 100%
Answer: (0%)
A 25-year-old man experiences severe intolerance to certain medications. On 2 occasions, his reactionsto various drugs have necessitated hospital admission. His family pedigree with respect to this conditionis shown below, with the red arrow indicating his position within the family. Assume that this conditiondemonstrates complete penetrance and is rare in the general population. This condition most likelyexhibits which of the following inheritance patterns?
a.X-linked recessive
b.X-linked dominant
c.Autosomal dominant
d.Mitochondrial
e.Autosomal recessive
The pedigree shows that only males are affected by the drug intolerance. Specifically, male offspring ofunaffected parents are affected. There is no evidence of male-to-male transmission. This pattern is mostconsistent with X-linked recessive inheritance from an asymptomatic carrier female in the firstgeneration. In X-linked recessive inheritance:
1. Affected males will always produce unaffected sons and carrier daughters.
2. Carrier females have a 50% chance of producing an affected son or carrier daughter. G6PD deficiency,which causes acute hemolytic anemia on exposure to oxidant drugs, follows an X-linked recessivepattern of inheritance.
The correct answer is:
X-linked recessive
While examining a family pedigree for a condition you notice that none of the affected males have sonsthat are affected. What is the inheritance pattern of the condition?
a.The phenomenon is due to incomplete penetrance
b.Autosomal dominant
c.Mitochondrial
d.The phenomenon is due to imprinting
e.Autosomal recessive
The correct answer is:
Mitochondrial
Huntington’s disease is due to which of the following mutations?
a.Silent mutation
b.Nonsense mutation
c.Trinucleotide repeat
d.Missense mutation
e.Chromosomal deletion
HD is an autosomal dominant disease caused by degeneration of striatal neurons and characterized bya progressive movement disorder and dementia. Jerky, hyperkinetic, sometimes dystonic movementsinvolving all parts of the body (chorea) are characteristic; affected individuals may later developbradykinesia and rigidity. The disease is relentlessly progressive and uniformly fatal, with an averagecourse of about 15 years. The gene for HD, HTT, located on chromosome 4p16.3, encodes a 348-kDprotein known as huntingtin. In the first exon of the gene, there is a stretch of CAG repeats that encodesa polyglutamine region near the N terminus of the protein. Normal HTT genes contain 6 to 35 copies ofthe repeat; when the number of repeats is increased beyond this level, it is associated with disease.
The correct answer is:
Trinucleotide repeat
Which of the following techniques involves the application of distinct DNA sequences resulting in manyidentical copies sufficient for analysis?
a.Northern blot
b.Southern blot
c.Dot blot
d.Western blot
e.Polymerase chain reaction (PCR)
PCR provides a means of amplifying distinct DNA sequences, starting with incredibly tiny amounts ofDNA and resulting in large amounts of identical copies sufficient for analysis. PCR is sensitive enough toamplify the DNA from a single cell to yield amounts sufficient for analysis. PCR requires prior knowledgeof sequence information at the two ends of the target sequence. PCR needs primers to start DNAsynthesis, which means that some DNA sequence in or close to the region of interest must be known.
The correct answer is:
Polymerase chain reaction (PCR)
To analyse DNA, first, we need to remove the histones and do DNA fragmentation. Within thefragments is the gene or sequence of our interest. What is the next immediate step in the blottingtechnique after the DNA fragments are generated by restriction enzymes?
a.Electrophoresis
b.Autoradiography
c.Hybridization
d.Addition of primer
e.Probing
What is the central dogma of genetics?
a.protein–>RNA–>DNA
b.DNA–>mRNA–>protein
c.RNA–>DNA–>protein
d.mRNA–>DNA–>protein
e.DNA–>protein–>mRNA
The incidence of Duchenne muscular dystrophy in North America is about 1/3,000 males. Based on this,what is the gene frequency of this X-linked recessive mutation?
a.2/3,000
b.1/9,000
c.1/6,000
d.(1/3,000)2
e.1/3,000
Because males have only a single X chromosome, each affected male has one copy of the disease-causing recessive mutation. Thus, the incidence of an X-linked recessive disease in the male portion of a population is a direct estimate of the gene frequency in the population.
The correct answer is:
1/3,000
Triple test performed on a pregnant woman at 18 weeks of gestation reveals low levels of alpha-fetoprotein (AFP). Amniocentesis confirms these findings. The mother is a known alcoholic and smoker.
Low AFP levels are associated with which of the following conditions?
a.Trisomy 21
b.Neural tube defects
c.Turner syndrome
d.Omphalocele
e.Fetal alcohol syndrome
The correct answer is:
Trisomy 21
A single missense mutation in the gene coding for cystathionine beta-synthase causes a variety ofphenotypic manifestations including skeletal deformities, mental retardation and vascular thromboses.
This phenomenon is referred to as:
a.Polyploidy
b.Variable penetrance
c.Segregation
d.Imprinting
e.Pleiotropy
Cystathionine beta-synthase deficiency is the enzyme defect present in classic homocystinuria.Homocystinuria is characterized clinically by ectopia lentis, mental retardation, marfanoid habitus andosteoporosis in addition to vascular problems. Pleiotropy is the occurrence of multiple phenotypicmanifestations, often in different organ systems, as a result of a single genetic defect. Pleiotropydescribes instances where multiple phenotypic manifestations result from a single genetic mutation.Most syndromic genetic illnesses exhibit pleiotropy. Polyploidy occurs when more than two completesets of homologous chromosomes exist within an organism or partial hydatidiform mole, for example,there are cells of nonstandard ploidy (typically 69XXX, 69XXY or 69 XYY). The chromosomes in this caseare derived from one haploid maternal set and two haploid paternal sets of chromosomes. Penetrancerefers to the proportion of individuals with a given genotype that express the associated phenotype. Inincomplete penetrance, less than 100% of individuals with a given genotype express its associatedphenotype. The law of segregation (Mendel’s first law) describes the phenomenon wherebygametogenesis within the parent organism results in the separation of paired chromosomes and thusthe separation of paired 31 genes so that each offspring inherits only half of each parent’s geneticcomposition Parental imprinting refers to the preferential transcription of genes from one or another ofa homologous pair of chromosomes depending on the parental origin of the chromosome.
The correct answer is:
Pleiotropy
In studying a large number of families with a small deletion in a specific chromosome region, it is noted that the disease phenotype is distinctly different when the deletion is inherited from the mother as opposed to the father. What is the most likely explanation?
a.Mitochondrial inheritance
b.X-linked recessive inheritance
c.Sex-dependent penetrance
d.Imprinting
e.X-linked dominant inheritance
Imprinting refers to the differential transcriptional activity of genes inherited from the father versus themother. Under mitochondrial inheritance, only an affected mother can transmit the disease phenotype;the offspring of affected males are always unaffected. The other modes of inheritance can influence therelative proportions of affected individuals who belong to one gender or the other (e.g., more affectedmales under X-linked recessive inheritance, more affected females under X-linked dominantinheritance), but they do not involve any differences in expression depending on the transmittingparent.
The correct answer is:
Imprinting
Non-invasive prenatal screening (NIPS) is a highly accurate screening test. What does it measure?
a.cfDNA of the fetus
b.Maternal DNA
c.The presence of neural tube defect
d.Amniotic fluid
e.The gestational age
Non-invasive prenatal screening (NIPS), used for common autosomal and sex chromosomeaneuploidies possible, with sensitivities and specificities approaching 99% for trisomy 21. After 9-10weeks post LMP, the serum of a pregnant woman contains fetal DNA that is not contained in thenucleus of a cell but is floating freely in the maternal circulation. Significant proportion (5 - 50 %) of allcfDNA found in maternal plasma. Short pieces of DNA. Commercial kits and PCR to isolate and prepareDNA for analysis.
The correct answer is:
cfDNA of the fetus
Which of the following statements is CORRECT regarding autosomal recessive inheritance?
a.Male are more frequently affected than females
b.Females are more frequently affected than males
c.Affected individuals are not seen in every generation
d.Clinical expression results from heterozygous allele inheritance
The correct answer is:
Affected individuals are not seen in every generation
Topic 1 - Cellular Structure and Function
TLO 1.1: Identify cellular organelles and describe each of their functions
Nucleus:
Controls cellular activities and houses genetic material.
Topic 1 - Cellular Structure and Function
TLO 1.1: Identify cellular organelles and describe each of their functions
Mitochondria:
Produce energy through ATP synthesis
Topic 1 - Cellular Structure and Function
TLO 1.1: Identify cellular organelles and describe each of their functions
Endoplasmic Reticulum:
Rough ER synthesizes proteins; smooth ER synthesizes lipids.
Topic 1 - Cellular Structure and Function
TLO 1.1: Identify cellular organelles and describe each of their functions
Golgi Apparatus:
Modifies, packages, and distributes cellular products.
Topic 1 - Cellular Structure and Function
TLO 1.1: Identify cellular organelles and describe each of their functions
Lysosomes
Contain digestive enzymes for breaking down cellular waste.
Topic 1 - Cellular Structure and Function
TLO 1.1: Identify cellular organelles and describe each of their functions
Peroxisomes
Involved in oxidation reactions, particularly fatty acid breakdown.
Topic 1 - Cellular Structure and Function
TLO 1.1: Identify cellular organelles and describe each of their functions
Ribosomes
Site of protein synthesis.
TLO 1.1: Identify cellular organelles and describe each of their functions
Vacuoles
Storage organelles for various substances.
TLO 1.1: Identify cellular organelles and describe each of their functions
Chloroplasts (in plant cells):
Responsible for photosynthesis.
TLO 1.1: Identify cellular organelles and describe each of their functions
Cell Membrane
Controls what enters and exits the cell.
Topic 1 - Cellular Structure and Function
TLO 1.2: Explain the basis of the fluid mosaic model of biological membranes and relate the structure to its function
The fluid mosaic model describes cell membranes as a phospholipid bilayer with embedded proteins. Key features:
Phospholipid bilayer
Forms the membrane’s basic structure.
Topic 1 - Cellular Structure and Function
TLO 1.2: Explain the basis of the fluid mosaic model of biological membranes and relate the structure to its function
The fluid mosaic model describes cell membranes as a phospholipid bilayer with embedded proteins. Key features:
Fluidity:
Allows lateral movement of membrane components.
Topic 1 - Cellular Structure and Function
TLO 1.2: Explain the basis of the fluid mosaic model of biological membranes and relate the structure to its function
The fluid mosaic model describes cell membranes as a phospholipid bilayer with embedded proteins. Key features:
Embedded proteins:
Perform various functions (e.g., transport, signaling).
Topic 1 - Cellular Structure and Function
TLO 1.2: Explain the basis of the fluid mosaic model of biological membranes and relate the structure to its function
The fluid mosaic model describes cell membranes as a phospholipid bilayer with embedded proteins. Key features:
Cholesterol
Regulates membrane fluidity and stability.
Topic 1 - Cellular Structure and Function
TLO 1.2: Explain the basis of the fluid mosaic model of biological membranes and relate the structure to its function
The fluid mosaic model describes cell membranes as a phospholipid bilayer with embedded proteins. Key features:
Glycoproteins and glycolipids
Form the glycocalyx for cell recognition.
Topic 1 - Cellular Structure and Function
TLO 1.2: Explain the basis of the fluid mosaic model of biological membranes and relate the structure to its function
The fluid mosaic model describes cell membranes as a phospholipid bilayer with embedded proteins. Key features:
This structure enables selective permeability, cell signaling, and maintenance of cell shape.
Topic 2 – Molecules of Life
TLO 2.1: Identify the four major macromolecules in the human body and their sources
Proteins
Sourced from dietary amino acids.
Topic 2 – Molecules of Life
TLO 2.1: Identify the four major macromolecules in the human body and their sources
Lipids
Sourced from dietary fatty acids and glycerol.
Topic 2 – Molecules of Life
TLO 2.1: Identify the four major macromolecules in the human body and their sources
Carbohydrates
Sourced from dietary simple sugars.
Topic 2 – Molecules of Life
TLO 2.1: Identify the four major macromolecules in the human body and their sources
Nucleic Acids
Sourced from nucleotides synthesized in the body or from diet.
Topic 2 – Molecules of Life
TLO 2.2: Describe the major roles of proteins in the human body
Proteins serve as:
- Structural components (e.g., collagen)
- Enzymes catalyzing biochemical reactions
- Transport molecules (e.g., hemoglobin)
- Hormones (e.g., insulin)
- Antibodies for immune function
- Cell signaling receptors
- Muscle contraction components (actin and myosin)
Topic 2 – Molecules of Life
TLO 2.3: Describe the major roles of lipids in the human body
Lipids function as:
- Energy storage (triglycerides)
- Cell membrane components (phospholipids and cholesterol)
- Insulation (subcutaneous fat)
- Hormone precursors (steroid hormones)
- Facilitators of fat-soluble vitamin absorption
- Cell signaling molecules (lipid-based second messengers)
Topic 2 – Molecules of Life
TLO 2.4: Describe the major roles of carbohydrates in the human body
Carbohydrates serve as:
- Primary energy source (glucose)
- Energy storage (glycogen)
- Structural components (e.g., ribose in nucleic acids)
- Cell recognition molecules (glycoproteins and glycolipids)
- Dietary fiber for digestion and gut health
Topic 2 – Molecules of Life
TLO 2.5: Describe the major roles of nucleic acids in the human body
Nucleic acids (DNA and RNA) are crucial for:
- Genetic information storage (DNA)
- Protein synthesis (mRNA, tRNA, rRNA)
- Gene regulation (miRNA and other regulatory RNAs)
- Enzyme cofactors (e.g., NAD+ and FAD in metabolism)
Topic 2 – Molecules of Life
TLO 2.6: Discuss how dysfunction of macromolecules can result in disease
Macromolecule dysfunction can lead to various diseases:
Proteins
Misfolding (e.g., Alzheimer’s) or enzyme deficiencies (e.g., Phenylketonuria)
Topic 2 – Molecules of Life
TLO 2.6: Discuss how dysfunction of macromolecules can result in disease
Macromolecule dysfunction can lead to various diseases:
Carbohydrates
Impaired glucose metabolism (diabetes) or glycogen storage diseases
Topic 2 – Molecules of Life
TLO 2.6: Discuss how dysfunction of macromolecules can result in disease
Macromolecule dysfunction can lead to various diseases:
Lipids
Cholesterol imbalance (atherosclerosis) or lipid storage disorders (e.g., Tay-Sachs)
Topic 2 – Molecules of Life
TLO 2.6: Discuss how dysfunction of macromolecules can result in disease
Macromolecule dysfunction can lead to various diseases:
Nucleic Acids
Genetic mutations (e.g., sickle cell anemia) or DNA repair defects (increased cancer risk)
Topic 3 – Cell Transport
TLO 3.1: Identify cellular transport mechanisms used by a cell to move substances across the membrane and discuss factors that determine the type of transport used
Transport mechanisms:
Passive transport
Simple diffusion, facilitated diffusion, osmosis
Topic 3 – Cell Transport
TLO 3.1: Identify cellular transport mechanisms used by a cell to move substances across the membrane and discuss factors that determine the type of transport used
Transport mechanisms:
Active transport
Primary active transport, secondary active transport
Topic 3 – Cell Transport
TLO 3.1: Identify cellular transport mechanisms used by a cell to move substances across the membrane and discuss factors that determine the type of transport used
Transport mechanisms:
Vesicular transport
Endocytosis, exocytosis
Topic 3 – Cell Transport
TLO 3.1: Identify cellular transport mechanisms used by a cell to move substances across the membrane and discuss factors that determine the type of transport used
Transport mechanisms:
Factors determining transport type
- Concentration gradient
- Molecule size and polarity
- Membrane permeability
- Energy requirements
- Presence of specific transport proteins
Topic 3 – Cell Transport
TLO 3.2: Explain the differences between passive and facilitated diffusion
Passive diffusion:
- Molecules move directly through the phospholipid bilayer
- No energy required
- Limited to small, nonpolar molecules
Topic 3 – Cell Transport
TLO 3.2: Explain the differences between passive and facilitated diffusion
Facilitated diffusion:
- Requires transport proteins (channels or carriers)
- No energy required
- Allows passage of larger or polar molecules
- Can be regulated by the cell
Topic 3 – Cell Transport
TLO 3.3: Explain the difference between primary and secondary active transport using relevant clinical examples
Secondary active transport
- Uses energy from electrochemical gradient created by primary active transport
- Example: Glucose-sodium cotransporter (SGLT) in kidney tubules (glucose reabsorption)
Topic 3 – Cell Transport
TLO 3.3: Explain the difference between primary and secondary active transport using relevant clinical examples
Primary active transport
- Directly uses ATP for energy
- Example: Na+/K+ ATPase pump in neurons (maintains resting membrane potential)
Topic 4 – Cell Cycle and Cell Division
TLO 4.1: Describe the stages of the cell cycle and the important functions that take place within each one
Interphase
- G1: Cell growth and preparation for DNA synthesis
- S: DNA replication
- G2: Preparation for mitosis
Topic 4 – Cell Cycle and Cell Division
TLO 4.1: Describe the stages of the cell cycle and the important functions that take place within each one
Mitotic phase
- Mitosis: Nuclear division
- Cytokinesis: Cytoplasmic division
Topic 4 – Cell Cycle and Cell Division
TLO 4.1: Describe the stages of the cell cycle and the important functions that take place within each one
G0 phase
Quiescent or senescent state (optional)
Topic 4 – Cell Cycle and Cell Division
TLO 4.2: Explain the process of mitosis and describe the important events that take place in each phase
Prophase
Chromatin condenses, nuclear envelope breaks down, spindle fibers form
Topic 4 – Cell Cycle and Cell Division
TLO 4.2: Explain the process of mitosis and describe the important events that take place in each phase
Metaphase
Chromosomes align at the metaphase plate
Topic 4 – Cell Cycle and Cell Division
TLO 4.2: Explain the process of mitosis and describe the important events that take place in each phase
Anaphase
Sister chromatids separate and move to opposite poles
Topic 4 – Cell Cycle and Cell Division
TLO 4.2: Explain the process of mitosis and describe the important events that take place in each phase
Telophase
Chromosomes decondense, nuclear envelopes reform, cytokinesis begins
Topic 4 – Cell Cycle and Cell Division
TLO 4.3: Identify the different types of stem cells in the human body and the structures they can potentially become (unipotent, pluripotent, multipotent and totipotent), and relate their function to therapeutic potential
Totipotent
Can form all cell types (e.g., zygote)
Topic 4 – Cell Cycle and Cell Division
TLO 4.3: Identify the different types of stem cells in the human body and the structures they can potentially become (unipotent, pluripotent, multipotent and totipotent), and relate their function to therapeutic potential
Pluripotent
Can form most cell types (e.g., embryonic stem cells)
Topic 4 – Cell Cycle and Cell Division
TLO 4.3: Identify the different types of stem cells in the human body and the structures they can potentially become (unipotent, pluripotent, multipotent and totipotent), and relate their function to therapeutic potential
Multipotent
Can form multiple cell types within a lineage (e.g., hematopoietic stem cells)
Topic 4 – Cell Cycle and Cell Division
TLO 4.3: Identify the different types of stem cells in the human body and the structures they can potentially become (unipotent, pluripotent, multipotent and totipotent), and relate their function to therapeutic potential
Unipotent
Can form only one cell type (e.g., spermatogonial stem cells)
Topic 4 – Cell Cycle and Cell Division
TLO 4.3: Identify the different types of stem cells in the human body and the structures they can potentially become (unipotent, pluripotent, multipotent and totipotent), and relate their function to therapeutic potential
Therapeutic potential
Regenerative medicine, tissue engineering, disease modeling, drug screening.
Topic 4 – Cell Cycle and Cell Division
TLO 4.4: Justify the importance of maintaining balance between cell division and apoptosis
Balancing cell division and apoptosis is crucial for:
- Tissue homeostasis
- Proper organ function
- Prevention of cancer and other diseases
- Embryonic development
- Immune system regulation
Topic 4 – Cell Cycle and Cell Division
TLO 4.5: Describe the process of meiosis
Meiosis consists of two divisions:
Meiosis I
Homologous chromosomes pair, crossover, and separate
Topic 4 – Cell Cycle and Cell Division
TLO 4.5: Describe the process of meiosis
Meiosis consists of two divisions:
Meiosis II
Sister chromatids separate
Topic 4 – Cell Cycle and Cell Division
TLO 4.5: Describe the process of meiosis
Meiosis consists of two divisions:
Results in four haploid gametes with genetic diversity.
Topic 4 – Cell Cycle and Cell Division
TLO 4.6: Compare meiosis to mitosis
Similarities:
- Both involve DNA replication and cell division
Topic 4 – Cell Cycle and Cell Division
TLO 4.6: Compare meiosis to mitosis
Differences
- Meiosis produces haploid gametes; mitosis produces identical diploid cells
- Meiosis involves two rounds of division; mitosis involves one
- Meiosis includes genetic recombination; mitosis does not
- Meiosis occurs only in germ cells; mitosis occurs in somatic cells
Topic 5 – Introduction to the Genome
TLO 5.1: Describe the major components that make up the human genome
Nuclear DNA
23 pairs of chromosomes
Topic 5 – Introduction to the Genome
TLO 5.1: Describe the major components that make up the human genome
Mitochondrial DNA
Circular DNA in mitochondria
Topic 5 – Introduction to the Genome
TLO 5.1: Describe the major components that make up the human genome
Genes
Protein-coding sequences
Topic 5 – Introduction to the Genome
TLO 5.1: Describe the major components that make up the human genome
Regulatory elements
Promoters, enhancers, silencers
Topic 5 – Introduction to the Genome
TLO 5.1: Describe the major components that make up the human genome
Non-coding DNA
Introns, repetitive sequences
Topic 5 – Introduction to the Genome
TLO 5.1: Describe the major components that make up the human genome
Telomeres
Protective end sequences of chromosomes
Topic 5 – Introduction to the Genome
TLO 5.2: Identify the major enzymes involved in DNA replication and their functions
DNA helicase
Unwinds the DNA double helix
DNA primase
Synthesizes RNA primers
DNA polymerase III
Main replicative enzyme, extends DNA strands
DNA polymerase I
Removes RNA primers, fills gaps
DNA ligase
Joins Okazaki fragments
Topic 5 – Introduction to the Genome
TLO 5.3: Compare and contrast the process of DNA replication in eukaryotic and prokaryotic cells
Differences
- Eukaryotic replication is slower and more complex
- Eukaryotes have multiple origins of replication; prokaryotes have one
- Eukaryotes replicate linear chromosomes; prokaryotes replicate circular DNA
- Eukaryotes have telomere maintenance; prokaryotes do not
Topic 5 – Introduction to the Genome
TLO 5.3: Compare and contrast the process of DNA replication in eukaryotic and prokaryotic cells
Similarities
- Both use semiconservative replication
- Both require similar enzymes (helicases, polymerases, ligases)
Topic 5 – Introduction to the Genome
TLO 5.4: Explain the process of transcription and translation in a eukaryotic cell
Transcription:
- Initiation: RNA polymerase binds to promoter
- Elongation: RNA synthesis
- Termination: RNA release
- Post-transcriptional modifications: 5’ capping, 3’ polyadenylation, splicing
Topic 5 – Introduction to the Genome
TLO 5.4: Explain the process of transcription and translation in a eukaryotic cell
Translation:
- Initiation: Ribosome assembly on mRNA
- Elongation: Amino acid chain formation
- Termination: Release of completed protein
- Post-translational modifications: Folding, chemical modifications
Topic 6 – Cell Signaling and Communication
TLO 6.1: Define the term receptor and identify the different membrane proteins that can act as receptors
A receptor is a protein that binds to a specific signaling molecule, triggering a cellular response. Membrane proteins acting as receptors:
- G protein-coupled receptors (GPCRs)
- Receptor tyrosine kinases (RTKs)
- Ion channel-linked receptors
- Enzyme-linked receptors
Topic 6 – Cell Signaling and Communication
TLO 6.2: Identify and explain the roles of the major receptor types
- G protein-coupled receptors (GPCRs): Signal transduction through G proteins
- Receptor tyrosine kinases (RTKs): Phosphorylation of target proteins
- Ion channel-linked receptors: Direct ion flow across membranes
- Enzyme-linked receptors: Catalyze intracellular reactions
Topic 6 – Cell Signaling and Communication
TLO 6.3: Explain the role of proteins in cell signaling and communication
Proteins play crucial roles in cell signaling:
- Receptors: Detect and respond to signals
- Signal transducers: Relay and amplify signals
- Enzymes: Modify other proteins
- Scaffold proteins: Organize signaling complexes
- Transcription factors: Regulate gene expression
- Ion channels: Control ion flow and membrane potential
Topic 6 – Cell Signaling and Communication
TLO 6.4: Distinguish between endocrine, paracrine and autocrine signaling mechanisms and the types of transduction pathways that can be activated
Endocrine signaling: Long-distance communication via bloodstream
Paracrine signaling: Short-distance communication between nearby cells
Autocrine signaling: Cell signals to itself. Transduction pathways:
1. cAMP pathway
2. Phosphoinositide pathway
3. JAK-STAT pathway
4. MAP kinase pathway
Each signaling mechanism can activate various transduction pathways depending on the specific receptor and ligand involved.
Topic 7 – Enzyme Function and Classification
TLO 7.1: Explain the basic principles of enzyme function
Enzymes are biological catalysts that:
- Lower activation energy of reactions
- Exhibit substrate specificity
- Remain unchanged after catalysis
- Function optimally under specific conditions (pH, temperature)
- Can be regulated by various factors
Topic 7 – Enzyme Function and Classification
TLO 7.2: Describe the properties of enzyme kinetics
Key properties of enzyme kinetics include:
- Michaelis-Menten kinetics
- Km (Michaelis constant) and Vmax (maximum velocity)
- Lineweaver-Burk plot for determining kinetic parameters
- Effects of substrate concentration on reaction rate
- Enzyme saturation
Topic 7 – Enzyme Function and Classification
TLO 7.3: Describe the different classifications of enzymes and their relative function
Enzyme classifications:
- Oxidoreductases: Catalyze oxidation-reduction reactions
- Transferases: Transfer functional groups between molecules
- Hydrolases: Catalyze hydrolysis reactions
- Lyases: Add or remove groups without hydrolysis
- Isomerases: Catalyze intramolecular rearrangements
- Ligases: Join two molecules using ATP hydrolysis
Topic 7 – Enzyme Function and Classification
TLO 7.4: Identify key enzyme inhibitors and their clinical relevance
- Competitive inhibitors: Compete with substrate for active site (e.g., statins inhibiting HMG-CoA reductase)
- Non-competitive inhibitors: Bind to allosteric site (e.g., aspirin inhibiting cyclooxygenase)
- Irreversible inhibitors: Permanently modify enzyme (e.g., penicillin inhibiting bacterial cell wall synthesis)
- Suicide inhibitors: Enzyme converts inhibitor to reactive form (e.g., acyclovir inhibiting viral DNA polymerase)
Topic 8 - Cellular Biochemistry
TLO 8.1: Justify the use of glucose as the body’s primary energy source
Glucose is the primary energy source because:
Glucose is the primary energy source because:
1. It’s readily available from carbohydrate digestion
2. It can be quickly metabolized for energy
3. All cells can use it
4. It can be stored as glycogen for later use
5. It’s essential for brain function
TLO 8.2: Identify the locations of bioenergetic reactions in the cell
- Cytoplasm: Glycolysis
- Mitochondrial matrix: Krebs cycle, fatty acid oxidation
- Inner mitochondrial membrane: Electron transport chain, oxidative phosphorylation
- Endoplasmic reticulum: Lipid synthesis
- Peroxisomes: Fatty acid oxidation (very long-chain fatty acids)
TLO 8.3: Define aerobic and anaerobic metabolism and provide bioenergetic examples of each
Aerobic metabolism: Requires oxygen for complete oxidation of substrates
Example: Complete glucose oxidation through glycolysis, Krebs cycle, and electron transport chain.
Anaerobic metabolism: Occurs without oxygen
Example: Lactic acid fermentation during intense exercise
TLO 8.4: Explain the major steps and products of glycolysis, Krebs cycle and the Electron Transport Chain (ECT)
Glycolysis:
1. Glucose → 2 Pyruvate
2. Net production: 2 ATP, 2 NADH
Krebs cycle:
1. Acetyl-CoA → 2 CO2
2. Per cycle: 3 NADH, 1 FADH2, 1 GTP
Electron Transport Chain:
1. NADH and FADH2
TLO 8.5: Identify the key enzymes and steps in glycogen metabolism
Key enzymes in glycogen metabolism:
- Glycogen synthase: Adds glucose units to glycogen
- Glycogen phosphorylase: Breaks down glycogen to glucose-1-phosphate
- Branching enzyme: Creates branch points in glycogen
- Debranching enzyme: Removes branch points during glycogen breakdown
Steps:
- Glycogenesis: Glucose → Glucose-6-phosphate → Glucose-1-phosphate → UDP-glucose → Glycogen
- Glycogenolysis: Glycogen → Glucose-1-phosphate → Glucose-6-phosphate → Glucose (in liver) or pyruvate (in muscle)
TLO 8.6: Provide clinical examples of metabolism disorders
- Diabetes mellitus: Impaired glucose metabolism
- Phenylketonuria: Phenylalanine metabolism disorder
- Glycogen storage diseases: Impaired glycogen metabolism
- Fatty acid oxidation disorders: e.g., Medium-chain acyl-CoA dehydrogenase deficiency
- Urea cycle disorders: e.g., Ornithine transcarbamylase deficiency
TLO 8.7: Describe the sequence of reactions involved in the oxidation of fatty acids in the mitochondrion and its regulation
Fatty acid oxidation (β-oxidation):
- Activation: Fatty acid → Fatty acyl-CoA
- Transport into mitochondria via carnitine shuttle
- β-oxidation cycle:
a. Dehydrogenation (FAD → FADH2)
b. Hydration
c. Dehydrogenation (NAD+ → NADH)
d. Thiolysis (CoA-SH) - Acetyl-CoA enters Krebs cycle
TLO 8.7: Describe the sequence of reactions involved in the oxidation of fatty acids in the mitochondrion and its regulation
Regulation:
- Inhibited by high levels of acetyl-CoA and NADH
- Stimulated by glucagon and epinephrine
- Inhibited by insulin
TLO 8.8: Describe the pathway for activation and transport of fatty acids to the mitochondrion for catabolism
- Activation: Fatty acid + CoA + ATP → Fatty acyl-CoA + AMP + PPi
- Carnitine shuttle:
a. Fatty acyl-CoA + Carnitine → Fatty acyl-carnitine + CoA
b. Transport across inner mitochondrial membrane
c. Fatty acyl-carnitine + CoA → Fatty acyl-CoA + Carnitine - Fatty acyl-CoA enters β-oxidation cycle
TLO 8.9: Explain the rationale for the pathway of ketogenesis and identify the major intermediates and products of this pathway
Rationale: Ketogenesis occurs when glucose is scarce and fatty acid oxidation is high, providing alternative fuel for the brain.
Pathway:
1. Acetyl-CoA → Acetoacetyl-CoA
2. Acetoacetyl-CoA + Acetyl-CoA → HMG-CoA
3. HMG-CoA → Acetoacetate
4. Acetoacetate → β-hydroxybutyrate or Acetone
Major intermediates: Acetoacetyl-CoA, HMG-CoA
Major products: Acetoacetate, β-hydroxybutyrate, Acetone (ketone bodies)
TLO 8.10: Describe the three mechanisms used by humans for removal of nitrogen from amino acids before the metabolism of their carbon skeletons
- Transamination: Transfer of amino group to α-ketoglutarate, forming glutamate
- Oxidative deamination: Removal of amino group as ammonia by glutamate dehydrogenase
- Urea cycle: Conversion of ammonia to urea for excretion
TLO 8.11: Outline the sequence of reactions in the urea cycle including key regulatory steps
Urea cycle steps:
1. Carbamoyl phosphate synthesis
2. Citrulline formation
3. Argininosuccinate synthesis
4. Argininosuccinate cleavage
5. Arginine cleavage to urea
Key regulatory steps:
* Carbamoyl phosphate synthetase I (rate-limiting)
* N-acetylglutamate (allosteric activator)
TLO 8.12: Define the terms and give examples of glucogenic and ketogenic amino acids
Glucogenic amino acids: Can be converted to glucose
Examples: Alanine, Aspartate, Glutamate
Ketogenic amino acids: Can be converted to ketone bodies
Examples: Leucine, Lysine
Some amino acids are both glucogenic and ketogenic (e.g., Phenylalanine, Tyrosine)
TLO 8.13: Summarise the sources and use of ammonia in animals, and explain the concept of nitrogen balance
Sources of ammonia:
1. Amino acid deamination
2. Bacterial action in the gut
3. Glutamine breakdown in the kidney
Uses of ammonia:
1. Urea synthesis
2. Glutamine synthesis
3. Nucleotide synthesis
Nitrogen balance: The state where nitrogen intake equals nitrogen excretion. Positive balance indicates growth or tissue repair, while negative balance suggests catabolism or inadequate protein intake.
TLO 8.14: Identify the essential amino acids and the metabolic sources of the nonessential amino acids
Essential amino acids (cannot be synthesized by humans):
Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine
Nonessential amino acids
(can be synthesized):
Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, Tyrosine
Metabolic sources of nonessential amino acids:
- Transamination of keto acids
- Conversion from other amino acids
- Synthesis from metabolic intermediates (e.g., 3-phosphoglycerate for serine)
