Physiology Exam Reviewer PDF

MODULE 1: Introduction to Physiology Objective 1: Definition and Scope of Physiology & Importance of Studying Physiology and Understanding Life Processes What is Physiology? ​ Deals with function and mechanisms of living organisms ​ Provides insights into the complex processes that sustain life...

MODULE 1: Introduction to Physiology Objective 1: Definition and Scope of Physiology & Importance of Studying Physiology and Understanding Life Processes What is Physiology? ​ Deals with function and mechanisms of living organisms ​ Provides insights into the complex processes that sustain life ​ 2 Types: ○​ Animal Physiology: how animals survive, grow, and reproduce ○​ Plant Physiology: studies the processes that enable plants to grow, reproduce, and adapt Key Concepts in Physiology ​ Functionality ○​ How biological systems and structures function to maintain life or survive ​ Animals: how the heart pumps blood, how the brain processes information ​ Plants: how plants synthesize bioactive compounds ​ Homeostasis ○​ The ability of an organism to maintain a stable internal environment despite external fluctuations ​ Animals: regulate temperature ​ Plants: balance water ○​ Makes sure everything is in equilibrium ○​ E.g.: Oxygen saturation ​ Oxygen baseline = 98 ​ During exercise, it decreases; after exercise, it goes back to baseline ​ Levels of Organization ○​ Cellular Physiology ​ Activities within individual cells ​ A metabolic activity that occurs within cells can affect the human body as a whole ○​ Tissue Physiology ​ How groups of cells function collectively or as a group ​ 4 Major Types of Tissue: Epithelial, Muscular, Connective, Nervous ○​ Systemic Physiology ​ Tissues work together; explores the function of organ systems ​ 11 Organ Systems: ○​ Organismal Physiology ​ Looks at how entire organisms operate and adapt to their environment ​ Looks at the organism as a whole, and how they respond to various stimuli ​ Comparative Physiology ○​ Similarities and differences in physiological processes across different species Key Areas of Animal Physiology ​ Respiration System ○​ Animals take in O2 and release CO2 via respiratory system ○​ CO2 accumulation makes blood acidic → CO2 as waste or byproduct → blood won’t become acidic ○​ Mechanisms: ​ Mammals: lungs ​ Fish: gills ​ Insects: trachea ​ Circulatory System ○​ Transports O2, nutrients, and hormones to cells and removes waste products ​ Vertebrates: closed circulatory system ​ Invertebrates: (some) open circulatory system ​ Nervous and Endocrine Systems ○​ Both are responsible for coordination and control ○​ Nervous System: quick responses to stimuli via electric signals ​ Sensory (afferent) Neurons (SN): deliver signals to the brain ​ Motor (efferent) Neurons (MN): deliver signals from brain to the muscles and glands ○​ Endocrine System: long term processes through hormones  ​ Hormones are transported via the bloodstream (long duration) ​ E.g.: growth and reproduction ​ Thermoregulation ○​ Animals maintain body temperature via mechanisms ​ Humans: sweating (evaporation of sweat cools body temperature) ​ Dogs: panting ​ Reptiles: basking in the sun ○​ Contracted muscles → release heat → high body temperature → activated sweat glands → release water → dehydration ​ Digestive System ○​ Converts food into energy and nutrients ○​ Carnivores, herbivores, and omnivores have specialized adaptations to process different diets Key Areas of Plant Physiology ​ Photosynthesis ○​ Plants convert light energy into chemical energy in the form of glucose ○​ Occurs in chloroplasts via chlorophyll, H2O, and CO2 ​ Transport System ○​ Xylem: conducts water and dissolved minerals from root to leaves ○​ Phloem: distributes sugars and other organic compounds throughout plant ​ Water Regulation ○​ Plants regulate water through transpiration and stomata control ○​ Root systems adapt to optimize water absorption ​ Too much water = cell will not burst due to cell wall ○​ Type of soil determines nutrient content of plants ​ Soil loss (agricultural issue): leads to less nutrients in plants ​ Growth and Hormones ○​ Growth is regulated by hormones ​ E.g.: auxins, gibberellins, and cytokinins ○​ Tropisms allow plants to respond to environmental stimuli ​ Shoots mobilize towards light (phototropism) ​ Roots grow deeper in response to gravity (gravitropism) ​ Reproductive Physiology ○​ Sexual Reproduction: flowers, pollen, and seeds ○​ Asexual Reproduction: occurs via structures such as runners (horizontal roots) or tubers (root plant) Interdependence of Life through Plants and Animals Trophic Pyramid ​ Animals rely on plants for O2 and food [Result of photosynthesis] ​ Plants depend on animals for pollination, seed dispersal, and nutrient recycling (decomposition) Applications of Physiology ​ Medicine: fundamental to diagnosing and treating diseases ​ Agriculture: informs crop improvement, irrigation practices, and pest control ​ Environmental Science: help assess the impact of environmental changes on organisms [air quality, trophic system] ​ Biotechnology: manipulating physiological processes has led to advancements in genetic engineering and pharmaceutical Objective 2: Homeostasis: Mechanisms and Significance in Plants and Animals Homeostasis is Related to our Multicellularity ​ One of our characteristics is our multicellularity: multicellular organisms must maintain homeostasis ○​ Living organisms have an ability to maintain homeostasis, but a challenge due to multicellularity ​ On a cellular level,  ○​ The amount of extracellular fluid (ECF) and intracellular fluid (ICF) should be balanced (isotonic) ​ Concentration of electrolytes + amount of fluid outside and inside the cell should be balanced ​ If imbalance, our cells would die—soon affecting our organs ○​ Interstitial fluid ​ External to cells [ECF] — fluid between cells ​ O2 (external) → inhale → lungs—alveoli (internal) → diffuse O2 to capillaries, then cells → production of glucose → energy → exhale CO2 Skin (Epidermal strata) ​ Outermost layer of the epidermis are dead cells ​ 3 Layers: ○​ Epidermis: avascular (no blood supply) ​ Actively dividing via mitosis ​ Stratum basale: receives sufficient supply of nutrients via diffusion process by blood capillaries ​ No nucleus due to being dry; but cheek cells have a nucleus due to being in a moist environment ○​ Dermis: vascular ○​ Subcutaneous layer Blood Vessels ​ For transporting nutrients ​ For diffusion of gas ​ Fenestration: fenestrated capillaries are tiny blood vessels (have small pores in them), which increase the flow of nutrients, waste, and other substances; they allow them to move from capillaries to the organs surrounding them ○​ Fenestrae: present in blood vessels walls as pores where nutrients pass through ​ Too much ECF = edema (increase in fluid between cells) ○​ Lymph vessels will collect excess ECF (interstitial fluid) to maintain homeostasis ​ During transport process, some components of blood plasma leak → result in ECF and ICF imbalance ○​ Interstitial or lymphatic fluid: leaked substances ○​ An excess interstitial fluid enters the lymph vessels or lymph ​ Lymph vessels: present partners of each blood capillary ○​ Collects the excess ECF accumulating within the cells ○​ Ensures fluid content (inside and outside) are in equilibrium ​ Interstitial fluid (blood plasma component) will be transported back to the blood vessels [blood should be clean] ​ Lymph nodes; ○​ Filter the plasma (contains WBC to fight infections) ○​ Filter lymph (containing excess interstitial fluid—if in lymph vessels, called lymphatic fluid) before returning to blood vessels ○​ If not, contamination in blood will spread Body Factors Regulated Homeostatically ​ Concentration of nutrients; O2 and CO2; colts and electrolytes ​ pH range ​ Blood volume and blood pressure ​ Body temperature Life Maintains Internal Consistency ​ Ability to sense or react to stimuli [recall: homeostasis] ​ Homeostasis is regulated by Automatic Control System (ACS) ○​ 3 ACS Factors: ​ Sensor: responds to stimuli, which is transported to CC by SN; can detect changes ​ Control Center (CC): interprets signals by sensor (SN) and coordinates response ​ Thermoregulator in brains transport interpreted signals to the effector via MN ​ Effector: follows the command of CC and performs action ​ E.g.: sweat glands (MN)  ○​ Exercise → increase body temperature → sweat → decrease water vol in blood → decrease urine output → produce heat → increase HR → increase BP = NFL Negative Feedback Loop (NFL) ​ Cycle of events in which our body’s internal condition is monitored, evaluated, modified, re-monitored, and re-evaluated ​ Make sure the body is balanced or back to homeostasis ​ E.g.: increase in glucose levels → there will be opposite response to go back to homeostasis ★​ 37°C: optimum temperature for body enzymes ○​ 37°C < thermal energy = denaturation ○​ Proteins: have folding activities* ★​ Glucose level ar 90 mg/100 mL NFL Case 1: Blood Glucose Level Rise Due to Eating a Cupcake (stimulus) ​ Stimulus → saliva will cause initial digestion of carbohydrates due to salivary amylase (converts into sugar) → move to esophagus for peristalsis (peristaltic contractions → partial digestion of proteins in stomach (converts into acidic chyme) and absorption of water and alcohol (directly into bloodstream) → move to small intestine for final digestion, absorption of nutrients, and conversion of complex carbohydrates to glucose → sugar is absorbed in body as glucose → blood glucose level rises → signal transported to the brain (sensor) → CC coordinates response → transfer signals to pancreas → (effector organ) pancreas distributes insulin → liver takes up glucose and stores it as glycogen and body cells take up glucose → decline in blood glucose levels = homeostasis ○​ Stomach: 1.2 pH level [high HCl] ​ Protected by mucus from mucus cells ​ Mucus cells: can be destroyed by Helicobacter pylori–causing the stomach lining damage = ulcer ​ Empty stomach and ingestion of alcohol → fast absorption of alcohol into bloodstream ​ Food + alcohol = slower absorption of alcohol into bloodstream ○​ Small intestine: duodenum, jejunum, and ileum (connected to large intestine) ○​ Glucose: fuel of body cells ○​ Insulin: helps initiate for glucose to enter the cell from the bloodstream ​ Beta cells in pancreas: found in islets of Langerhans ​ Islets of Langerhans: produces insulin ○​ Microvilli: increase surface area for absorption ​ Question: What about excess glucose in the body? ○​ Will be stored in the liver as glycogen → to contribute in decreasing blood glucose level ​ Can also be stored in skeletal muscle ○​ Glycogen: complex carbohydrate; stored energy in animals ○​ Starch: plants counterpart ​ Question: What happens if we have no pancreas that is functional? ○​ Result: Type I Diabetes ​ Type I Diabetes: Beta cells are not capable of producing insulin ​ Juvenile onset; can be hereditary or diagnosed at early age ​ Body attacks beta cells ○​ No beta cells to produce insulin → glucose won’t enter the cells → no energy ○​ Accumulation of glucose in blood → damage to organs → Diabetes mellitus ​ Question: What happens if we develop Type II Diabetes? ○​ Type II Diabetes: stops the body from using insulin properly → leading to high levels of blood sugar, if not treated ​ Beta cells are capable of producing insulin  ​ Maturity onset; involves diet & lifestyle; common in obese people ​ Due to high fat content contributing to insensitivity, non-binding of insulin to receptors ​ Receptors specific to body cells where insulin binds develop resistance or insensitivity to insulin ​ If the receptors become resistant to insulin, glucose level will rise ​ Recommendation: change diet & exercise → to help reduce blood glucose level ​ High protein diet → takes longer for proteins to be converted into glucose NFL Case 2: Blood Glucose Levels Decrease Due to Lack of Eating (stimulus) ​ Blood glucose level decreasing → alpha cells in pancreas release glucagon → liver breaks down glycogen via glycolysis and release glucose into the bloodstream → rise in blood glucose level to normal = homeostasis ​ Main source of energy: carbohydrates; Secondary source: fats – Interconnectedness of Different Organ Systems – ​ Digestive System absorbs nutrients, salt, and water → goes to Circulatory System → releases waste from cellular respiration (CO2) + DS releases physical wastes + Urinary System filtering blood, reabsorb necessary nutrients, and eliminating excess water and salt (metabolic wastes) ​ CS transports nutrients and O2, then delivers O2 to different organ systems producing ATP NFL Case 3: Decrease in Blood Pressure & Fluid Volume Renin-angiotensin System ​ Stimuli: drop in BP and fluid volume [will require too much pressure from the heart] ​ Renin: enzyme released from kidney ​ Angiotensinogen: protein secreted by liver; precursor of Angiotensin I ○​ Kidney releases Renin, which converts Angiotensinogen into Angiotensin I ​ Angiotensin I: ○​ Lungs produce Angiotensin-converting Enzyme (ACE), which converts Angiotensin I to Angiotensin II ​ Angiotensin II: ○​ Will act on Adrenal Gland (above the kidney) to stimulate release of Aldosterone ○​ Acts directly on blood vessels stimulating vasoconstriction ​ Vasoconstriction: constriction/narrowing of blood vessels, which increases BP ​ Aldosterone: ○​ Acts on kidney to stimulate reabsorption of NaCl and H2O (reabsorption of NaCl ions and thus attracts H2O as the NaCl concentration in the bloodstream increases) ​ Pituitary Glands releases Antidiuretic Hormone (ADH) to kidney ​ Result: blood volume and BP going up ​ Question: What if a patient has hypertension? ○​ Block ACE by utilizing medicines with ACE inhibitors → there will be no release of Angiotensin II and Aldosterone → blood volume and BP won’t go up NFL Case 4: Hypoxia (a region of the body is deprived of O2 at tissue level) ​ Hypoxia: decrease in number of RBC or erythrocytes → decrease in hemoglobin count → low level of O2 in body tissues ​ Erythropoietin (EPO) Mechanism: ○​ Stimulus: low RBC count → decreased availability of O2 ○​ EPO: released by kidney (effector) and sometimes liver; stimulates Red Bone Marrow to produce more RBC [Erythropoiesis] → increase O2 carrying capacity of blood → homeostasis ​ Erythropoiesis: body’s process of making RBC or erythrocytes  ​ People who live in highlands have higher RBC content due to low O2 present in the area NFL Case 5: Blood Ca2+ Levels ​ Ca2+: for bone development and muscle contractions ○​ Normal level: ~9 mg/100 mL ​ Stimulus: Blood Ca2+ levels decrease ○​ Parathyroid glands (posterior to thyroid glands): release Parathyroid hormones (PTH) ○​ PTH: ​ Stimulates release of Ca2+ from bones ​ Ca2+ release: due to osteoclasts ○​ Osteoclast: bone-destroying cells ○​ Osteoblast: bone-forming cells ​ Stimulates reabsorption of Ca2+ into the blood by the kidneys ​ Stimulates activation of Vitamin D synthesized by the skin (Integumentary System) ​ Ca2+ cannot be utilized without Vit D that absorbs calcium ​ Stimulus: Blood Ca2+ levels increase ○​ Thyroid gland: produces calcitonin (hormone) ​ Osteoblasts are activated ○​ Bone remodelling → maintain blood Ca2+ level and our anatomical structure ​ Interconnected actions of osteoblast and osteoclast = Ca2+ level regulation NFL Case 6: SNS Centers ​ Smoking → constriction of blood vessels → person will look older + more prone to hypertension Positive Feedback Loop ​ Change in a given direction causes additional change in the same direction ○​ E.g.: an increase in the concentration of a substance causes feedback that produces continued increases in concentration ​ Amplifies initiating stimuli ​ Moves system away from its starting state PFL Case 1: Pregnancy ​ Stimulus: during contractions, the baby inside pushes its head against the cervix ○​ Uterus is lined with smooth muscles → causes contractions ○​ Contractions from cervix serve as a signal → transported to the brain (CC), coordinating the response → brain stimulates pituitary gland to secrete hormone oxytocin → oxytocin travels to the uterus via bloodstream → uterine contractions are amplified ​ Oxytocin: hormone produced by hypothalamus, which amplifies uterus contractions ​ More uterus contractions (baby pushes against the cervix more) → more signals sent to the brain → release of oxytocin → increase in uterine contractions → repeat ​ Question: What happens after the baby is born? ○​ Since baby is not connected to the placenta anymore, breast milk is produced for breastfeeding ​ Activation of mammary glands (duct: baby sucking nipples) → brain signal pituitary gland to secrete prolactin ​ More breastfeeding = more prolactin produced ○​ Transfer to bottled (fortified) milk, when mother’s prolactin declines due to less prolactin release PFL Case 2: Blood Clotting ​ Low blood volume = low BP ​ Damage to blood vessels → stimulates production of platelets/thrombocytes → formation of platelet plugs → clot development  ​ Resting platelet → activated platelet → blood clot → produce stimuli to other platelet to create blood clot ○​ Putting pressure activates resting platelets 1.​ WBCs (immunity cell/leukocytes) flock to site of breakage to maintain body sterility → blocks pathogen entry via localization of infection [Inflammatory Response] ○​ Localized infection = Damaged tissues ○​ Diapedesis: histamine → increase in permeability of blood vessel walls → increased blood flow to site of infection (migration of WBCs to infection site) → increase in heat, causing redness → leakage of plasma and proteins, causing swelling → pain 2.​ Activation of Platelets 3.​ Clot is surrounded by Fibrin strands ○​ Fibrin: meshy structure PFL Case 3: Hemostasis (blood clots to stop blood loss) ​ Stoppage of blood flow ​ Result of a break in a blood vessel (which is a smooth muscle) ○​ Simple squamous tissue: capable of filtration ​ Three (3) Phases: 1.​ Vascular Spasm 2.​ Platelet Plug Formation 3.​ Coagulation (blood clotting) ​ Atherosclerosis: accumulation of fat in blood vessel—disrupting blood flow ​ Haemophilia: common blood disorder for type A and B ○​ “Royal blood” Disorder ○​ Its abnormality: absence of specific clotting factors ​ Type A: no clotting factor VII ​ Type B: no clotting factor IX ​ Stimulus: vessel injury ○​ Vessel injury → vascular spasm → platelet plug formation → clot formation ​ Scar formation: indicative broken connective tissue in the dermis ​ [picture on the right] ○​ Prothrominase turns prothrombin to thrombin; ○​ Thrombin converts fibrinogen to yellow fibrin strands; ○​ Threadlike structures in clotting from fibrin are formed ​ Question: What if an abnormal blood clot forms—blocking blood flow? ○​ Block to heart = heart attack [Myocardial Infarction (MI)] ○​ Block to brain = stroke [Cardiovascular Accident (CVA)] PFL Case 4: Pyrexia (fever) ​ Pyrexia: raised body temperature; fever; systemic inflammation ​ Question: What happens when one has a fever? ○​ Body temperature increases as a response to infection → increases metabolism → immune system cells are activated → repeating until fever breaks ​ Increased metabolism: only good to an extent, as it affects the immune cells to do their job effectively; however, if body temperature increases too high, death can occur ○​ There is an inflammatory response ○​ Once sweating begins, body goes back to normal temperature (lower) ​ Fever Categories: ○​ Low grade: 37.3°C - 38°C ○​ Moderate grade: 38.1°C - 39°C ○​ High grade: 39.1°C - 41°C ○​ Hyperthermia: > 41°C [harder for cells to survive] ​ Question: How does fever occur?  ○​ PGE2 Activation: exogenous pyrogens stimulate endogenous pyrogens to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) → to transfer signals from blood to the brain and raise the core body temperature ○​ Exogenous pyrogens: bacteria, viruses ​ Exposure to exogenous pyrogens ​ LPS: gram negative bacteria/lipopolysaccharide ○​ ExogenousP binds to leukocytes through a receptor ​ Specifically to the macrophages [Antigen Presenting Cell (APC)] ​ Macrophages: engulf antigens and present them to other WBCs ○​ Endogenous pyrogens: cytokines (inflammatory proteins) ​ When activated, causes inflammation—a systemic inflammatory response ​ IL: interleukin; IFN: interferon; TNF: tumor necrosis factor ○​ Leukocytes are macrophages ​ APC ​ B cells ○​ T helper cells: produces antibodies to help fight the foreign pathogen ○​ Plasma cells ○​ B memory cells ○​ Circumventricular Organs (CVO) ​ CVO: point of communication between the blood, brain, and cerebrospinal fluid (CSF) ​ Location: around 3rd & 4th ventricles ​ OVLT: signals transferred from body to the brain, raising the core body temperature from contraction of underlying muscles ○​ Question: When we are sick or encountering foreign substances (bacteria/viral infections), why does our body temperature go up? ​ To activate the immune system, in order for the immune cells to attack unwanted organisms ​ Take medication to reduce the body temperature ​ Paracetamol → blocks PGE2 → hypothalamus doesn’t activate fever → reduces pain and lowers body temperature ​ Iron: sequestered by body so microbes can grow and multiply; why we feel “weak” when we are sick ​ Shivering: to contract smooth muscles to produce heat ○​ Pimples: example of inflammatory response ​ Caused by Staphylococcus aureus ​ S. aureus: should not be in bloodstream → may result in local inflammation (e.g.: pimple) ○​ Do not touch! There are blood vessels and can further infection of bacteria then go up to the brain ​ Inflamed tissue sends signals to neutrophils (granular leukocytes) ​ There is also a battle between the immune system and S. aureus: drying of pimple ○​ Cardinal Signs of Inflammation: 1.​ Rubor (redness): increased blood flow 2.​ Dolor (pain): secretion of prostaglandin ○​ Medications inhibit the secretion of prostaglandin to help alleviate the pain ○​ Way of body telling us not to touch the local site of inflammation, since it is in healing process 3.​ Calor (heat): increased blood pressure 4.​ Tumor (swelling): blood plasma leaks ○​ All four (4) signals are regulated by interleukins ○​ Blood vessel apparatus ​ Smooth muscle: to allow for movement; non striated structure of cells; involuntary control ​ Simple squamous epithelium lining: to allow for filtration ○​ Conclusion: The overall goal in response to fever is to bring leukocytes to a normal level PFL Case 5: Cytokine storm during COVID-19 Pandemic ​ Cytokine: proteins that help control inflammation in the body ​ Our bodies have first, second, and third line of defense: ○​ First: Skin: protects our body from the external environment ○​ Second: Fever ○​ Third: Immune system cells  ​ Virus gets inside → immune cells identify virus and produce cytokine by binding to APC → activation of exogenous pyrogen → cytokine recruit adaptive immune system → adaptive immune system cells secrete proinflammatory proteins or cytokine → causes systemic inflammation or fever ○​ Cytokine increases risk of stroke ​ Alveolus: for gas exchange ○​ Lined with simple squamous epithelium for ease of diffusion process ○​ Continuous exposure to COVID and thus cytokines ○​ Components of blood plasma accumulate in alveoli → alveolus compressed → lungs’ respiratory failure ​ Pneumocytes ○​ Type 1: thin squamous epithelium for gas exchange ○​ Type 2: synthesizing cells of surfactant ​ In severe coronavirus disease 2019 (COVID-19) patients, accumulation of cytokines is exaggerated resulting in a “cytokine storm,” in which aberrant cytokine expression and disproportionate inflammation result in persistent acute lung injury extending beyond the time of peak viral load. In the figure, it illustrates that, (1) coronavirus infects lung cells, (2) immune cells, including macrophages, identify the virus and produce cytokines, (3) cytokines attract more immune cells, such as white blood cells, which in turn produce more cytokines, creating a cycle of inflammation that damages the lung cells, and (4) damage can occur through the formation of fibrin, (5) weakened blood vessels allow fluid to seep in and fill the lung cavities, leading to respiratory failure. Physiology: From Cells to Systems [VIDEO] Cell ​ Blood vessels ​ Basic unit of life ​ Glands ​ ~200 cell types exist in the human body ​ Neurons ​ There are as many microbial cells as human cells Organ System ​ When organs work together Tissue ​ 11 Organ Systems DINERS CLIMER ​ Cells work together to form tissues 1.​ Urinary ○​ 4 Tissue Types: 2.​ Respiratory ​ Epithelial 3.​ Skeletal ​ Nervous 4.​ Reproductive ​ Muscle 5.​ Nervous ​ Connective 6.​ Muscular Organ 7.​ Lymphatic ★​ Small intestine 8.​ Endocrine ○​ Made up of: 9.​ Integumentary ​ Connective tissue 10.​ Circulatory ​ Muscle tissue 11.​ Digestive Homeostasis in Plants [VIDEO] Homeostasis ​ Can open and close depending on the environment, ​ Maintenance of a stable internal environment to help maintain homeostasis by maintaining gas ​ Occurs through two mechanisms: Negative and water levels within the plant feedback & Positive feedback ​ Help maintain homeostasis [example of negative feedback] Plants maintain homeostasis ○​ Open stomata – allow gases and water to ​ Plants cells work best if they have the correct come in and out of a plant temperature and water level ○​ Closed stomata – acts as a wall, water is ​ Plants maintain homeostasis through the use of held within the plant and gases are not their stomata exchanged ○​ Stomata are more likely to open when the Stomata plant is receiving enough water ​ Tiny holes in the leaves of plants ○​ Stomata are more likely to be closed during a drought Module 2: Cellular Physiology Objective 1: Membrane Potentials and Transport Mechanisms Organelles that Secrete Substances ​ Metabolism*: sum total of chemical reactions that occur in the body or in a cell ○​ Involved are various organelles (Table 1) ​ Smooth Endoplasmic Reticulum (SER): lipid and carbohydrate synthesis and drug detoxification (metabolic process) ​ Rough Endoplasmic Reticulum (RER): with presence of ribosomes for protein synthesis ​ Golgi Apparatus: for packaging & modification then transported Cellular Digestion Centers ​ Lysosomes: intracellular digestion ○​ Enzyme used: lysozyme ​ Vacuoles: for plants ​ Peroxisomes ○​ Hydrolytic process to hydrolyse ○​ Generate hydrogen peroxide, which they use for oxidative purposes ○​ Liver and kidney → detoxify Organelles that Extract Energy from Nutrients ​ Mitochondria: site of ATP synthesis ○​ Energy generator ○​ Genetics: Mitochondrial DNA (from the mother to child) ​ Same mitochondria from the mother (passed down and unchanged) Photosynthesis ​ Chloroplasts Table 1. Eukaryotic Organelles Divide Labor Extract Energy from Secrete Substances Cellular Digestion Centers Photosynthesis Nutrients Mitochondria (found in the Nucleus Lysosomes Chloroplasts liver, kidney, and muscles) Endoplasmic reticulum Vacuoles (SER/RER) Peroxisomes (commonly Golgi apparatus found in the liver) Cell Membrane Structure ​ Composed of phospholipid bilayer interspersed with proteins ​ Contains sterols like cholesterol to stabilize cell membrane ○​ Cholesterol: provides structural support; very integral in our cell membrane ​ Regulates membrane fluidity; important to regulate the substances across ​ Phospholipid Bilayer ○​ Composition: Bilayer, phospholipids consist of a hydrophilic (water-attracting) head and two hydrophobic (water-repelling) tails ○​ Hydrophilic heads face the cellular fluid ○​ Function: forms a semi-permeable barrier that controls the entry and exit of substances ​ Membrane has an extracellular side (outside the cell) and a cytoplasmic side (inside the cell) Lipid Bilayer ​ Two layers of phospholipids, cholesterol, and proteins ○​ Human body: extracellular is our internal environment ​ Contribute to the membrane's overall structure and functional properties ​ Allows lipid-soluble substances to enter the cell readily ○​ Each alveolus is composed of simple squamous epithelial tissues ○​ The exchange of gasses is very efficient because it’s only one layer. Selective Permeability: Crucial for Maintaining Homeostasis ​ Regulation of nutrient and ion transport ○​ The cell membrane controls the entry of essential nutrients (glucose, amino acids, O2) and exit of waste products (CO2and urea) ​ In each metabolic process, there is a waste product (CO2, urea) due to entry and exit of substances from a semipermeable membrane. ○​ Ion channels and transporters: regulate electrolyte balance (Na, K, Ca), essential for nerve impulses, muscle contraction, and fluid balance ​ Na: speeds up transport of nerve impulses which increases the heart rate. ​ K: causes relaxation; too much K can lead to death (heart will be slowed completely, as seen in euthanasia) ​ Ca: increase force of heart contraction; helps in movement of vesicles inside neurons ○​ Essential to maintain balance inside the cell ​ Protection and structural integrity ○​ Prevents harmful (unwanted) substances like toxins, viruses, and bacteria, from entering the cell ○​ Helps maintain the cell's shape and internal environment ○​ Regulates water transport and movement via aquaporins and preventing excessive swelling and shrinking of cells (will cause cell apoptosis) ​ Cell communication and signal transduction ○​ This function is essential for maintaining homeostasis ○​ Membrane receptors detect hormones, neurotransmitters, and other signalling molecules ​ Hormones have to be released (by endocrine cells) into the bloodstream; neurotransmitters (chemical substances secreted by neurons to communicate with each other) are much faster in terms of travelling ​ E.g.: acetylcholine neurotransmitter that causes contraction of skeletal muscles by binding ○​ Enables the cell to respond to external stimuli, regulating metabolism, immune responses and tissue repair ○​ Signal transduction: enables cells to respond to a stimuli 1.​ Reception 2.​ Transduction 3.​ Response ​ Energy production and metabolism ○​ Selective permeability allows controlled intake of glucose and O2, which are necessary for ATP production via cellular respiration in mitochondria ​ Osmoregulation and water balance ○​ Maintains proper fluid balance inside and outside cell (to avoid cell damage) ​ There should be a balance between the solute and solvent (such as water) concentrations ​ Cells are embedded in an isotonic solution because the amount of solute inside and outside the cell are in equilibrium ​ Neural and muscle function ○​ Innervation: process of supplying nerves to an organ or body part ​ Neurons and muscles are always tied together; a motor (efferent) neuron is always innervated to a skeletal muscle ​ Muscles are effector organs which receive signals from the CNS ○​ Sodium-potassium pump (Na+/K+ pump): ensures the proper electrical gradient for nervous impulse transmission  ​ Sodium ion (Na+) increases: ​ Heart rate and nerve impulses or transport of signals ​ Anesthetic agents block flow of sodium ions into the neurons ​ Potassium ions (K+): relaxes the heart ​ Flatline = influx of K ○​ Essential for muscle contraction and heartbeat regulation ​ RELAXATION: influx of potassium ion; too much potassium can be fatal ​ FASTER HEART BEAT: influx of sodium ions ​ Immune System Defense ○​ Selective permeability helps WBC recognize and attack foreign invaders ○​ Prevents autoimmune reactions by distinguishing self from non-self (foreign) ​ Autoimmune diseases: our cells attacking our own cells ​ Transplant rejection: need of immunosuppressive drugs Four (4) Main Parts of the Heart ​ Right Atrium: receiving chamber; receives deoxygenated blood from SVC and IVC ​ Left Atrium: receiving chamber; receives oxygenated blood from lungs ​ Right Ventricle: pumping chamber; pumps blood towards the lungs ​ Left Ventricle: pumping chamber; pumps blood towards the aorta → then to the body ○​ Aorta: carries blood away from your heart to the rest of the body Effects of Depletion of ATP ​ Cause: Ischemia (lack of blood flow) ○​ Blockage in blood flow; body subsequently does not get enough O2 → decrease in ATP production in mitochondria → leads to various issues Membrane Proteins ​ Integral Proteins: firmly embedded within the lipid bilayer; cannot be easily removed without disrupting the membrane involved in transport (channels and carriers for ions and molecules, signal transduction, receptors, cell adhesion) ○​ E.g.: Na-K channels, glucose transporters ○​ Channel Proteins: facilitate transport of ions and small molecules ​ Create hydrophilic pathways (passive transport–facilitated diffusion) ​ Non-gated Channel Proteins: remain open continuously permitting free flows of ions and H2O ​ Gated Channel Proteins: open or close in response to specific signals ​ To regulate amount of substances inside the cell ​ Crucial to processes (nerve signal transmission) ○​ Functions: ​ Transport ions (Na, K, Ca): maintain electrochemical gradients needed for cellular functions ​ Transport H2O: via aquaporins; facilitate rapid H2O movement across membranes; crucial for maintaining cellular hydration and volume ​ Peripheral Proteins: attached on membrane’s surface (outside the tails of lipid bilayer) ○​ Signaling and maintaining the cell’s shape, signal transduction, cell recognition ○​ Enzyme regulation, modulation of ion channels and receptors ​ Glycolipid: structural stability of cell membrane ○​ Helps maintain flexibility and fluidity of cell membrane ​ Facilitates transport of substances across the cell membrane ○​ Cell recognition: can identify different cell types ○​ Connecting cells to form tissues ○​ Functions as an energy source: can be converted into glucose derivatives ○​ Receptors: for specific hormones & neurotransmitters ​ Alpha-helix: biochemical and electrical signals transduction, molecular transport, energy propagation ○​ Interact between cells and the environment ○​ Electrical signal transduction: physical stimuli are converted into electrical signals ​ Glycoproteins: proteins + oligosaccharides ○​ Identification markers ○​ Cell recognition and communication ○​ Crucial for immune response  ○​ Receptors for hormones ○​ Signaling molecules: facilitate communication between cells) ○​ Cell adhesion: for formation of tissues and organs ○​ Protection ○​ Key role in reproduction: binding between sperm and egg cell ​ Cholesterol: support for membrane protein ○​ Membrane fluidity: maintaining optimal membrane integrity and flexibility ​ Humans are capable of synthesizing cholesterol ​ Carbohydrates ○​ Cell recognition and adhesion ○​ Determine blood groups ○​ Can trigger immune response ○​ Embryonic development ○​ Physical barrier on cell surface ○​ Attachment sites for pathogens ○​ Structural role ​ Globular Protein: ○​ Signal transduction ○​ Transport ○​ Cell-to-cell interactions ○​ Enzymatic catalysis ○​ Immune recognition ○​ Cellular homeostasis ○​ Communication Question: How does signal transduction work? 1.​ Reception: process by which a cell detects a signal in the environment 2.​ Transduction: process of activating series of proteins inside the cell from cell membrane 3.​ Response: change in behavior that occurs in the cell as a result of the signal Excitatory Neurons ​ Botulism: botulinum toxin ​ Tetanus toxin blocks glycine ○​ Glycine: for relaxation; if blocked, there will be detrimental effects Objective 2: Cell Signaling and Communication in Plants vs Animals Two (2) Types of Membrane Transport Type of Membrane Transport: Passive Transport: does not require energy ​ Purpose: to conserve energy ​ Diffusion and facilitated diffusion allow movement down the concentration gradient without energy expenditure ○​ Small nonpolar molecules (O2 and CO2), water (osmosis), charged ions (Na, K, Cl, glucose, amino acids) (facilitated diffusion), ethanol ​ Movement of substances across the cell membrane without requiring energy or ATP ​ Crucial for cellular functions: ○​ Homeostasis: maintaining stable internal environment necessary for proper cellular function ○​ Efficient resource management: ensures that essential nutrients and gases enter cells while waste products leave without requiring energy ○​ Cellular balance: aids in balancing osmotic pressure by facilitating water movement through osmosis via aquaporins, preventing cell swelling or shrinkage Type of Passive Transport: Simple Diffusion ​ Movement of substances from high to low concentration without assistance ○​ E.g.: ethanol entering bloodstream, exchange of gases in respiration ​ The direct movement of small nonpolar molecules across the lipid bilayer  ​ Occurs along the concentration gradient, from high concentration to low concentration ​ Important for gas exchange in lungs and tissues ​ Question: How does gas exchange relate to simple diffusion? ○​ O2 diffusion in the lungs (external respiration) ​ The concentration of O2 in the alveoli is higher than the capillary blood ​ Alveoli: site of gas exchange ○​ Lined with Pneumocytes I (simple squamous epithelial cells) ○​ Pneumocytes II: cells that produce surfactants; prevent alveoli from collapsing ○​ O2 concentration > CO2 ​ O2 molecules move passively from alveoli into the blood through the thin alveolar and capillary walls ​ Follows the concentration gradient (no energy needed—just the natural tendency of molecules to spread out evenly) ○​ CO2 diffusion in the lungs ​ CO2 concentration is higher in the blood capillaries than in alveoli since cells produce CO2 as waste product ​ CO2 diffuses out of the blood through the capillary wall into the alveoli, where it is exhaled ​ Respiration allows the release of waste products ○​ O2 and CO2 diffusion in body tissues (internal respiration) ​ Internal respiration: transfer of blood throughout the body ​ At the tissue level, O2 concentration is higher in the blood vessels than inside the cells, so O2 diffuses into the cells ​ Cells constantly produce CO2 during metabolism, so its concentration is higher inside the cells than in the blood ​ CO2 diffuses out of the cells into the bloodstream for blood vessels to transport it back into the lungs — ​ Pulmonary Circulation ○​ SVC to RA to RV to lungs (gas exchange) ○​ SVC carries deoxygenated blood from head to neck; IVC carries deoxygenated blood from the body (lower) ​ Systemic Circulation ○​ LV to arteries to capillaries (oxygenated blood) back to veins to RA to aorta — ​ The fat-soluble vitamins A, D, E, K are stored in the body for long periods of time and generally pose a greater risk for toxicity than water-soluble vitamins when consumed in excess. Eating a normal, well-balanced diet will not lead to toxicity in otherwise healthy individuals ○​ E.g.: emphysema ​ Lung disorder caused by destruction of alveoli wall due to the damage of pneumocytes II ​ Caused by exposure to toxic substances such as smoke Type of Passive Transport: Facilitated Diffusion ​ Uses carrier or channel proteins to help substances move ○​ E.g.: glucose entering cells ​ Movement of larger or polar molecules (glucose) via specific protein ○​ Channel proteins which bypass the lipid molecules and form pores for ions ○​ Carrier proteins change shape to transport molecules ​ Application/Question: How can glucose get transported to our cells via facilitated diffusion? ○​ Absorption from small intestine to blood and also from the lumen to the intestine ○​ Movement of glucose molecules across cell membranes with the help of carrier proteins ​ Carrier: GLUT2 transport protein ○​ How does GLUT work? ​ GLUT: glucose transporter; embedded in the plasma membrane ​ GLUT binds to glucose molecule to one side, undergoes a conformational change (allows glucose to pass through without directly interacting with the hydrophobic lipid bilayer)  ​ Glucose moves from areas of high concentration outside the cell to areas of low concentration (following its concentration gradient) ○​ Intestinal Lumen: where absorption of nutrients occurs ​ Hollow space within the intestine ​ Made up of villus (finger-like projections) to increase surface area ○​ Types of GLUT: present in different areas of the body ​ Non-insulin-dependent GLUT ​ GLUT1 (brain, erythrocytes, placenta) ​ GLUT2 (pancreas, kidney, liver) ​ GLUT3 (neuronal, placental) ​ Insulin-dependent GLUT ​ GLUT4 (skeletal muscle, heart, adipose tissue) ○​ Insulin: regulates the availability of glucose transporters ​ Transport from bloodstream to body cells 1.​ Responsible for GLUT4 recruitment: triggers a signaling cascade that leads to translocation of GLUT4 from intracellular vesicles to the cell membrane 2.​ Increases glucose uptake: a.​ Activation of GLUT4 attracts other GLUT b.​ Increase GLUT at the cell surface, enhances glucose uptake by facilitated diffusion, allowing more glucose to enter the cells when blood glucose levels are high c.​ If no insulin, glucose just keeps going in towards the blood capillaries i.​ Glucose remains in the blood because its entry isn’t permitted anymore for translocation 3.​ Regulation of transport activity: increases number of GLUT on the cell surface = increasing overall glucose uptake efficiency – Summary of Processes Involved in Glucose Transport – 1.​ Insulin binds to receptor 2.​ Signal cascade 3.​ Exocytosis 4.​ Glucose entry permitted ​ Application: Nerve Impulse Transmission ○​ Ion Channels ​ Nerve impulses rely on the rapid movement of ions, Na+ and K+, across neuronal membranes ​ Influx of Na+: speed up transmission of impulses ​ Efflux of K+: relaxation ​ Facilitated diffusion occurs through ion channels, which are proteins embedded in the membrane that form pores for these ions to pass through ○​ Action Potential Generation ​ At rest, neurons have a higher concentration of K inside and Na outside the cell ​ When stimulated, voltage-gated sodium channels open, allowing Na+ to rush into the cell via facilitated diffusion down the concentration gradient → this influx of positive charge depolarizes (activates) the membrane potential ​ If you don’t want to experience pain, use anesthetic agents ○​ Repolarization ​ As the action potential peaks, voltage-gated potassium channels open, facilitating K+ movement out of the cell down their concentration gradient through facilitated diffusion ​ Excitation is always followed by relaxation = maintains homeostasis ​ Muscles cannot always contract  ​ This efflux helps repolarize and eventually hyperpolarize the membrane before returning it to its resting state ○​ Role in Propagation ​ The rapid opening and closing of these ion channels allow nerve impulses to propagate along axons efficiently by creating a wave-like pattern of depolarization followed by repolarization – Myelin sheaths help in speeding the propagation of nerve impulses; damaging of myelin sheath results in slower propagation of impulses Type of Passive Transport: Filtration ​ Separate solids form liquids using hydrostatic pressure (pressure in blood vessel) ​ E.g.: filtration by kidneys during urine formation ○​ Destruction of blood vessels = disruption of filtration processes → push large molecules out of blood vessels → rupture of blood vessel ○​ Only amino acids can pass through fenestrae because they are small size; proteins are too large ○​ Protein is not normally present in urine ○​ Protein +++ → proteinuria ​ Application: Role of Kidneys in Filtration ○​ Main function: filter blood ○​ Occurs at the glomeruli (sing. glomerulus) within nephrons (~1.2 mill nephrons in each of the kidneys) ​ Kidney: located retroperitoneal (behind abdominal cavity) ​ Nephron: functional unit of kidney; filtering the blood, making sure blood is clean and free of waste substances ​ Composed of glomeruli & renal tubules ○​ Filters blood through blood pressure, which forces water and solutes (via hydrostatic force/pressure) through tiny pores into Bowman’s capsule or glomerular capsule ​ Glomerular capsule: initiates urine formation by removing waste products from the blood ○​ Importance of Capillary Filtration ​ Helps regulate fluid distribution between blood vessels and tissues ​ Ensures proper hydration of tissues while preventing excessive fluid buildup paces where it can be filtered or absorbed ​ Application: Hydrostatic Pressure in Kidneys ○​ E.g.: protein present in urine due to high hydrostatic pressure pushing protein out of capillary wall (proteinuria) ​ If the patient has protein in their urine, their blood pressure can be checked to explain this ​ High blood pressure → can lead to proteinuria Type of Passive Transport: Osmosis ​ Movement of water molecules across a semi permeable membrane from an area of lower solute concentration to an area of higher solute concentration ​ For maintaining fluid balance within the body ​ E.g.: dipping in beach → get thirsty because body cells are exposed to an isotonic solution ​ Water moves through a semi permeable membrane to equalize solute concentrations ​ Solute outside and inside the cell = equilibrium ○​ The best conditions for human cells are isotonic solutions ​ Question: How is osmosis applied in Human Physiology? ○​ Help maintain cellular integrity by regulating water content ○​ In isotonic conditions, cells neither swell nor shrink, which is essential for maintaining proper cellular function ○​ Intestinal Absorption: water absorption from the intestines into the bloodstream occurs via osmosis, aiding digestion, and nutrient uptake ○​ Kidney Function: the kidneys use osmosis to concentrate or dilute urine based on hydration levels and electrolyte balance ​ Osmosis: essential for maintaining proper fluid balance and electrolyte levels in the body through its action in kidney function  ​ Application: Role of Osmosis in Kidneys ○​ Water Reabsorption (back to the bloodstream) ​ Site: osmosis nephrons (respponsible for filtering waste and regulating fluid balance) ​ Components: glomerulus and tubule ​ After filtration by the glomerulus, water and solutes enter the renal tubule (semipremeable: allow water and small molecules to pass through while retaining larger molecules like proteins) ​ Water moves across this membrane based on concentration gradients—moving from areas with lower solute concentrations to areas with higher solute concentration until equilibrium is reached ​ Regulations by hormones: hormone vasopressin (antidiuretic hormone or ADH) regulates this process by adjusting permeability to water based on hydration status: when dehydrated, ADH increases permeability to retain more water ​ Amount of rehydration depends on hydration level of an individual ​ One molecule of Na attracts two molecules of H2O ​ Application: Importance of Nephrons in Biological Processes ○​ Different segments of the nephron contribute differently: ​ Proximal Convoluted Tubule (PCT): where most reabsorption occurs ​ Near point attachment ​ Secretion of creatinine: byproduct of muscle metabolism ​ Blood Urea Nitrogen (BUN): urea byproduct of ammonia metabolism ​ Loop of Henle: concentrates or dilutes urine depending on conditions ​ Collecting ducts: final adjustments under ADH influence ○​ *high creatinine levels in blood may be indicative of kidney issues ​ Question: What is IV Isotonic Solution for? ○​ Hypovolemia ○​ Raise blood pressure ○​ Mild Na depletion ​ Isotonic solutions have the same osmotic pressure as blood plasma ​ Ideal for intravenous (IV) administration without causing cell swelling or shrinking ​ Common isotonic solutions include 0.9% saline solution (normal saline), which maintains fluid balance without altering cellular osmolarity ​ Tonic capability of the solution to modify the volume of cells ​ Osmolarity: the number of particles of solute per liter of solution Type of Membrane Transport: Active Transport: requires energy ​ Active transport moves substances against their concentration gradient using energy Primary Active Transport ​ Uses ATP directly to transport molecules ​ E.g.: ATP-binding cassette (ABC) transporters move nutrients, such as sugars and amino acids ​ The sodium-potassium (Na+/K+) pump moves Na+ out of the cell and K+ into the cell against their gradients – PAT & Homeostasis – ​ The Na+/K+ ATPase pump helps maintain the resting membrane potential in nerve and muscle cells ​ Pumping 3 Na+ out and 2 K+ in ​ Prevents cell swelling, maintains electrical excitability, supports nerve impulses ​ This process ensures muscle contraction, heart function, and brain activity remain stable ​ Regulates ion balance, nerve signaling, and fluid balance, preventing conditions like hyperkalemia (excess K+) or hyponatremia (low Na+ levels) ​ The resting membrane potential is the stable electrical potential difference across the plasma membrane of a cell when it is not undergoing any significant electrical activity ○​ This potential is typically negative, meaning the inside of the cell is more negatively charged than the outside. In neurons, this value is usually ~70 mV Secondary Active Transport ​ Uses energy from one molecule moving down its gradient to transport another molecule against its gradient ​ Symporters move two substances in the same direction ○​ E.g.: glucose-Na+ co-transport in the intestines ​ Na+/Ca2+ exchanger in cardiac muscle cells – SAT & Homeostasis – ​ Uses the gradients set up by primary transport to move essential molecules like glucose, amino acids, and ions ​ E.g.: sodium-glucose co-transporter (SGLT) & blood sugar regulation ​ The SGLT (proteins) in the intestines and kidneys absorbs glucose using the Na+ gradient ​ This ensures glucose enters the bloodstream for energy while preventing excess glucose loss in urine ​ Question: What if disrupted? ○​ It can lead to hypoglycemia (low blood sugar) or diabetes-related complications because cannot enter from intestinal cell to the bloodstream ​ Maintains blood glucose levels, supports cellular energy production, and prevents nutrient imbalances Question: How do PAT and SAT work together for homeostasis? ​ PAT establishes ion gradients ​ SAT depends on these gradients to regulate nutrient absorption ​ Together, they maintain cell funcation, nervous system activity, and metabolic balance, ensuring overall homeostasis Cystic Fibrosis ​ Genetic disorder that primarily affects the lungs, pancreas, and other organs by causing thick, sticky mucus buildup ○​ Movement of water: mucus doesn’t become sticky ​ Caused by mutations in the CFTR (Cystic Fibrosis Tranmembrance Conductance Regulator) gene, which codes for a chloride ion channel found in the cell membranes of epithelial cells ○​ Chloride ion cannot get out → water also cannot get out → no gas exchange due to sticky mucus → sweat becomes salty ​ Question: Relation to Membrane Transport Mechanisms? ○​ CFTR protein: regulates the movement of chloride ions across the cell membrane ○​ Plays a crucial role in maintaining the proper balance of salt and water on epithelial surfaces, such as those lining the lungs and digestive tract Objective 3: Energy Metabolism Every single action in the body performances requires energy ​ The energy comes from cellular metabolism and respiration ​ The sum total of all reactions taking place in the body: understanding all this is fundamental to diagnosing and treating diseases Cellular Metabolism: the body’s biochemical engine ​ Cell metabolism: refers to all the biochemical reactions that occur within a cell to sustain life ○​ Catabolism: breaking down of molecules to release energy ○​ Anabolism: building complex molecules for growth and repair ​ Like the body’s economy ○​ Catabolism is earning money (ATP) and anabolism is spending it on necessary things (protein synthesis, DNA replication, and repair) Enzymes ​ Catalysts: chemicals that increase the rate of chemical reactions without becoming part of the products or being consumed in the reaction ​ 3D structures: creates specific-binding sites ​ Most enzyme are proteins, some are RNA (ribozymes) ​ One or more polypeptide chains ​ Active sites: formed by the arrangement of amino acids ​ Specialized sacs of enzymes: mitochondria, chloroplasts, lysosomes, peroxisomes  ​ Question: How does enzyme work? ○​ By lowering the amount of energy (activation energy) required to start a reaction ○​ An enzyme’s active site has a specific shape that binds to one or more substrates. After the reaction, the enzyme releases the products ​ Factors that affect enzyme activity: ○​ Temperature, pH, osmotic pressure ○​ Enzymes can become denatured and stop working ○​ One faulty enzyme can have dramatic effect ​ Cells control reaction rates ○​ Negative feedback (feedback inhibition ○​ Reaction’s product inhibit the enzyme that catalyzes the reaction ○​ As the reaction product accumulates, the reaction rate slows down ​ Overview of Feedback Inhibition ○​ Excess of product being produced → cell use feedback inhibition → slows down production → conserve energy → homeostasis ○​ Occurs when the biochemical product of a pathway blocks an enzyme in the beginning of the pathway ​ This occurs when there is a buildup of product/excess of the product being produced Key Metabolic Pathways ​ Carbohydrate Metabolism ○​ Glycolysis: the universal first step, breaking glucose into pyruvate ​ Pyruvate: producing ATP and NADH or nicotinamide adenine dinucleotide) ○​ Gluconeogenesis: the body’s backup plan to make glucose when fasting ○​ Clinical Relevance (Disruption of Cellular Metabolism): ​ Diabetes melitus → dysregulated glucose metabolism leads to hyperglycemia ​ Hyperglycemia → due to esxcess insulin or prolonged fasting can cause seizures or coma ​ Organ system involved: Nervous System ○​ Why: brain cells/neurons are dependent on glucose – no sufficient amount of glucose supply = no ATP ​ Disrupt the balance of neurotransmitters in the brain ​ Lipid Metabolism ○​ Beta-Oxidation: metabolic process that breaks down fatty acid to produce energy fatty acids → chopped into acetyl-CoA fueling ATP production ○​ Ketogenesis: emergency fuel production when glucose is scarce ​ E.g.: fasting, diabetes (because glucose cannot enter the cell; ketone will be the secondary source) ​ Synthesis of ketones to makeup for the scarcity of glucose [ketones = byproducts] ○​ Clinical Relevance: ​ Diabetic Ketoacidosis (DKA); uncontrolled fat breakdown produces excess ketones → leads to acidosis ​ Obesity and cardiovascular disease: lipid metabolism dysregulation leads to plaque formation in arteries ​ Protein Metabolism ○​ Amino acid catabolism: used for energy when ccarbohyddrates and fats are insufficient ○​ Urea cycle: converts toxic ammonia into urea for excretion ​ Urea: byproduct of protein metabolism ○​ Clinical Relevance: ​ Liver Failure (hepatic encephalopathy): ammonia build up leads to neurotoxicity and confusion ​ Possible cause: urea cycle disorder ​ Kwashiorkor and Marasmus ​ Kwashiorkor: prominent navel ​ Marasmus: prominent bones and decrease in subcutaneous fats ​ Protein malnutrition causes muscle wasting and immune dysfunction ​ Due to insufficient proteins ​ Prevalent in the PH Question: How do cells make energy? ​ Cellular Respiration: a multi step process that converts glucose and O2 into ATP ​ Powers every cell in the body  ​ 3 Stages of Cellular Respiration: 1.​ Glycolysis: occurs in the cytoplasm ○​ Splits glucose into pyruvate yielding ATP i.​ Pyruvate is essential to generate ATP ○​ Anaerobic energy source ○​ Can generate ATP in low oxygen conditions ○​ Pyruvate metabolize further (citric acid cycle or electron transport chain to synthesize more energy) i.​ Purpose: synthesize more ATP ○​ In the absence of O2, pyruvate converts to lactate i.​ Clinical Relevance: 1.​ Lactic acidosis – in O2-starved tissues (e.g. ischemia, sepsis), excess lactate causes acidosis (O2-starved tissues) 2.​ Cancer cells – rely on anaerobic glycolysis ○​ Glycolysis Terms: i.​ Pyruvate: key intermediate in biological processes (cellular respiration, fermentation, gluconeogenesis, fatty acid synthesis) ii.​ Acetyl CoA: coenzyme, key link iii.​ NADH: found in all living cells; involved in generating energy 2.​ Kreb’s Cycle ○​ Pyruvate is converted into Acetyl-CoA, generating NADH & FADH (Flavin Adenine Diculeotide) ○​ Yields CO2 ○​ Clinical Relevance: i.​ Mitochondrial disorders: 1.​ Defects in the Krebs cycle can lead to muscle weakness and neurodegeneration 2.​ Attributed to problems in ATP synthesis; since muscles are innervated by neurons → problems in neurotransmitters will subsequently affect the contraction of muscles 3.​ Electron Transport Chain (ETC) ○​ Uses O2 as the final electron acceptor to produce the bulk of ATP i.​ Generates water as a byproduct ○​ Clinical Relevance: i.​ Cyanide Poisoning 1.​ Blocks oxygen use in ETC, leading to rapid death 2.​ By binding to cytochrome C oxidase, blocking transfer of electrons to oxygen → inhibit ATP release ii.​ Hypoxia and Ischemia 1.​ Without O2, ATP production halts and causes cell death (e.g. stroke (CVA), heart attack (MI)) Question: What is the ultimate energy generator? ​ Oxygen O2 ○​ Essential for maximum ATP yield ○​ In low O2 conditions (hypoxia), cells switch to anaerobic respiration, producing lactate instead of ATP ​ This is why O2 therapy is used in COPD heart failure and carbon monoxide poisoning ○​ Rigor mortis → stiffness of death ​ No ATP produced due to lack of O2, so muscles will stay contracted CONCLUSION O2 IS VERY IMPORTANT GIRL! Question: What happens when metabolism goes wrong> ​ Metabolic Disorders: ○​ Diabetes Mellitus (Type 1 and 2) ​ Impaired insulin function prevents glucose uptake, forcing cells to burn fat and protein ​ Leads to hyperglycemia, polyuria, polydipsia, and ketoacidosis ​ Treatment → insulin therapy, glucose monitoring, and lifestyle changes ○​ Obesity and metabolic syndrome ​ Excess calorie intake disrupts lipid and glucose metabolism ​ Increases risk for hypertension, diabetes, and cardiovascular disease ​ Treatment → diet, exercise, pharamacotherapy (e.g.: metformin) → reduce glucose production in the liver Cellular Metabolism and Cellular Respiration → foundation of life and disease ​ A deep understanding of how cells produce energy will make you a better physician, researcher, or healthcare professional