Pathophysiology Quiz 1 Study Guide PDF

# Quiz 1: Altered Cellular and Tissue Biology This study guide has everything from the lectures I just organized it all so it makes sense in my brain. I'll explain tuesday :) # Cellular Adaptation: the cells response to escape and protect itself from injury There are 5 Types of Adaptive Changes:...

# Quiz 1: Altered Cellular and Tissue Biology This study guide has everything from the lectures I just organized it all so it makes sense in my brain. I'll explain tuesday :) # Cellular Adaptation: the cells response to escape and protect itself from injury There are 5 Types of Adaptive Changes: - **Atrophy:** ↓ in Cell Size and can refer to organ or a tissue - **Physiological:** e.g. early development babies have a large thymus that shrinks over time - **Pathologic:** occurs because of changes in blood supply, workload (e.g. use of muscles), nervous stimulation - **Hypertrophy:** Adaptive ↑ in Cell Size and can refer to an organ or a tissue. - In consequence it ↑ the size of affected organ - Sometimes used for compensation of an organ e.g. when one kidney is removed the other will show ↑ size of cells and the organ - **Physiological:** Cardiac and Skeletal muscles grow in response to an increased mechanical load and use. Reversible - **Pathologic:** In the heart, hypertrophy can manifest structural and functional ways that are secondary to hypertension, coronary artery disease, and valvular disease. Irreversible - **Hyperplasia:** ↑ Cell Number caused by an ↑ rate of cell division and can occur to organ or a tissue - Hyperplasia and hypertrophy occur at the same time a lot and both can happen in cells that can make DNA but it non-dividing cells only hypertrophy can occur - **Physiological:** Compensatory hyperplasia allows certain organs to regenerate (e.g. when part of the liver gets removed it can regenerate, or when the endometrium thickens prior to menstruation) - **Pathologic:** Abnormal proliferation of cells - **Metaplasia:** when one mature cell type gets replaced by another mature cell type. It is Reversible. - Involves reprogramming of the stem cells (non-specific) - Can occur in response to chronic irritation and inflammation (e.g. cigarette smoking causes chronic irritation and result in change in cells) - **Dysplasia:** deranged cell growth. AKA atypical hyperplasia. Abnormal changes in shape, size, organization, and nuclear features mature cells. - NOT considered a true adaptive process, related hyperplasia called Atypical Hyperplasia - Doesn't necessarily mean cancer but can progress to cancer - Always pathologic # Cell Injury: cell injury leads to injury of tissues and organs. - **Caused by:** - **Hypoxia:** insufficient oxygen supply - **Anoxia:** complete deprivation of Oxygen supply - Most common cause cell injury - In heart: Hypoxia → Ischemia → Injury → Infarct - In cell: Hypoxia → Reduced ATP production → Failure Na+/K+-ATPase and Sodium Calcium Exchanger → Na+ goes in K+ goes out Ca+ goes in → H2O follows Na+ → Cell fills up with water → *Cell Swelling* - Water coming into cell is MOST REVERSIBLE effect Hypoxia - In Cell: Lactic Acid Production - **Free Radicals** - **Reactive Oxygen Species (ROS):** (H2O2, ОН, О2) - Cause **Oxidative Stress** which imbalance between free radical generation and antioxidant defenses (not enough antioxidants combat all free radicals) *Also cause:* - Lipid Peroxidation → Cell Membrane Breakdown and lysis cell - Alteration protein folding - DNA Damage → Mutations - Created under Hypoxic conditions: Extremely unstable and reactive - **Internal Sources of ROS:** - Mitochondria - Ischemia - Inflammation - **External Sources of ROS:** - Smoking - Radiation - Ozone - Pollutants - **Reperfusion Injury** is when hypoxia results in production ROS and when blood flow restored the ROS break free from tissues/organ enter bloodstream and wreak havoc organs. (E.g. heart attack victims once blood flow restored the ROS cause arrhythmias, depressed contractile function) - **Chemical/Toxic Injury:** cause injury by: - **Direct Damage:** chemotherapy meds - **Overdose:** exaggerated response at target tissue/organ - **Toxicities:** Cyanide, hydrogen sulfide: bind Fe2+ in cytochrome oxidase mitochondria - Something like Carbon Monoxide (CO) has 300x greater affinity for Fe2+ in hemoglobin than O2. So hemoglobin will bind CO rather than O2 so your Hg won't carry oxygen muscles - **Biological Activation Toxic Metabolites:** The liver will try metabolize tylenol by turning into NAPQI which toxic - **Infection:** injuries caused infection. Infectious potential microorganism depends ability to: - Invade cause tissue destruction - Produce toxins - Produce damaging hypersensitivity reactions - **Immunological Inflammatory conditions:** injuries caused by: - Cellular chemical components immune/inflammatory membrane alterations - Complement damage causes water influx - Antibodies occupy membrane receptor molecules # Cell Injury can acute chronic - **Reversible Injury** means cell can recover. Ischemia (blood flow organ muscle reduced/restricted) (Caused hypoxia) - **Irreversible Injury** means cell will die. Infarct/necrosis (also caused hypoxia) # Systemic Signs Cell Injury: - Fatigue - Malaise - Fever - Altered Appetite - Leukocytosis (higher than normal WBC count) - ↑ Heart Rate - Pain # Cellular Accumulations: occur whenever: - Normal substances produced excess - Normal abnormal substances ineffectively catabolized → Harmful exogenous materials accumulate intracellular. - **Water:** cellular swelling (accumulation water) most common type degenerative change caused shift extracellular water into cells - **Hypoxia** one main causes this. Hypoxia → Reduced ATP production → Failure Na+/K+-ATPase and Sodium Calcium Exchanger → Na+ goes K+ goes out Ca+ goes in → H2O follows Na+ → Cell fills up with water → *Cell Swelling* - Most reversible type cellular accumulation - **Calcium:** normally calcium has low concentration inside cell cytoplasm stored mitochondria endoplasmic reticulum - Ca2+ acts second messenger when cell gets stimulated - Causes muscle contraction - Activates various enzymes - In **Hypoxia** Ca2+ will ↑ cytosol (media cell) → turns intracellular enzymes → intracellular structures can damaged - Uncontrolled entry calcium into cytosol final common pathway many causes cell death - **Dystrophic (dying tissue) Calcifications:** occurs dead dying tissues areas necrosis - Heart valves - Tumors - **Metastatic (widespread) Calcifications:** mineral deposits occur normal tissue result hypercalcemia - Hyperparathyroidism, toxic levels vitamin D, bone tumors - **Lipids:** accumulation lipids typically due metabolic disorders seen spleen, liver, CNS. - **Metabolic:** Tay-sachs disease, Niemann-Pick - **Steatosis:** Fatty transformation liver cells - **Atherosclerosis:** “hardening arteries” - **Carbohydrates:** Glycogen storage diseases - **Urate:** aka Uric Acid manifests Gout # Cell Death: - **Apoptosis:** programmed/regulated cell death “taking out trash” - **Necrosis:** unregulated cell death caused injuries cells - Cells swell rupture - Inflammation results - Depending what tissue's function will define type necrosis may susceptible to: - **Coagulative:** tissue firm. Gets pale - Seen Infarcts (areas tissue dead) any tissue except brain - Protein denaturation - **Liquefactive:** tissue liquid creamy yellow - Seen brain infarctions (stroke) infections - Cells essentially get digested their enzymes, liquifying tissue - **Caseous:** tissue white, soft, cheesy looking - Seen TB (lungs) - combo coagulative liquefactive necrosis - **Fat Necrosis:** tissue chalky, white areas - Seen acute pancreatitis where damaged acinar cells pancreas release Lipases → splits triglycerides fat cells → produces fatty acids combine with Ca2+ → soap formed - **Fibrinoid Necrosis:** vessel walls thickened pinkish red - Immune structural complexes fibrin deposited vessel walls - Type 3 hypersensitivity reaction: contact dermatitis - **Gangrene Necrosis:** large area necrotic tissue occurs due ischemia - Seen when limb loses blood supply dies loops bowel - **Dry Gangrene:** Hypoxic event lack arterial blood supply but venous blood flow still carries fluid out tissue - Tissue dry firm, shrivel - Tissue coagulates - **Wet Gangrene:** Hypoxic event lack venous blood supply fluid builds up tissue - Plump swells - Tissue tends undergo liquefactive necrosis with bacterial infection - **Gas Gangrene:** wet gangrene but C. Perfringens infection produces toxins crackling joint # Pain: # Nociception: the processing potentially harmful stimuli through normally functioning nervous system - 4 Phases: - **Transduction (our phone rings):** tissue gets damaged by exposure noxious stimuli stimuli gets converted electrophysiological signal aka nerve impulse - **Transmission (pass phone):** conduction impulse along delta and C fibers dorsal horn spinal cord then brainstem, thalamus, cortex - **Perception (I acknowledging phone ringing):** conscious awareness pain, affected emotions thoughts - **Modulation (answering putting phone silent):** physiologic process suppressing facilitating transmission pain signals throughout nervous system - **Neurotransmitters Pain Modulation:** - **Pain Inhibitors (suppress pain perception):** - GABA Glycine inhibit pain spinal cord - **Endogenous (made body) Opioids:** these morphine-like neuropeptides - Endorphins, endomorphins - Inhibit pain impulses periphery, spinal cord, brain - Endocannabinoids - Serotonin norepinephrine inhibit pain medulla pons - **Pain Facilitator (enhance pain perception)** - **Excitatory Neurotransmitters** CNS/PNS - Glutamate - Calcitonin - Aspartate - **Inflammatory Neurotransmitters** - Histamine - Prostaglandins - Bradykinin # Neuroanatomy Pain: - **Nociceptors:** First Order Neurons. Initiate Pain - Nociceptors: have bare nerve endings skin, muscle, joints, arteries, viscera respond noxious stimuli 3 Types: - Mechanical - Thermal - Chemical - **Myelinated A-delta:** larger others, transmission fast, very localized, sharp (burn pinprick) - Can initiate spinal reflex before pain received - **Unmyelinated C Fibers:** Numerous, transmission slower, poorly localized transmits dull ache burning sensation - Both these fibers terminate neurons dorsal horn - **Inhibitory Excitatory Interneurons:** Very short Second Order Neurons transmit impulse third order neurons which located anterior gray horn same level spinal cord - Can excitatory inhibitory - They function pain gate regular pain transmission - **Projection Neurons:** located spinothalamic tracts can second Third Order - Cross over spinal cord ascend - Carry signals brain - **Lateral Spinothalamic Tracts:** - **Neospinothalamic tract** - Carries fast impulse acute sharp pain - **Paleospinothalamic tract** - Carries slow impulses dull chronic pain temperature # Gate Control Theory: nerve impulses encounter pain gates reaching brain - **Descending inhibitory pathway** - **Inhibitory neurotransmitters** - Gates more closed - Fewer messages get through less pain experienced Excitatory neurotransmitters - Gates more open - More messages get through one experiences more pain # Clinical Description Pain: - **Pain Threshold:** point which stimulus perceived pain, lowest intensity pain person can recognize - **Pain Tolerance:** greatest intensity pain person can endure - ↓ repeated exposure. fatigue, apprehension - ↑ persistent use opioids, alcohol, distracting activities, faith - **Perceptual Dominance:** pain one location may cause increase threshold another location - person can have many painful sites but will only report most painful site - After dominant pain diminished person may then identify other painful areas - **Segmental Pain Inhibition:** Reducing pain through motion, myelinated A-beta fibers stimulated impulses arrive same spinal level impulses other fibers → they stimulate inhibitory interneuron decrease pain transmission (e.g rubbing injured area relieve pain) # Acute Pain: - Acute Pain protective mechanism - Alerts individual condition experience causing immediate harm body - Lasts less 3 months - **Clinical Manifestations:** Many mimic sympathetic nervous response - Tachycardia - Hypertension - Diaphoresis - Dilated Pupils # Chronic Pain: - Chronic pain serves purpose poorly understood. Causes suffering - Appears out proportion observable tissue injury - Lasts longer 3-6 months - Thought caused dysregulation nociception pain modulation processes CNS PNS - Persistent Chronic Pain leads physiological adaptation - Even though there still underlying stress body there can Normalized heart rate BP - Can cause behavioral psychological changes such cognitive deficits, depression, difficulty sleeping, eating problems - **Chronic Pain Syndromes:** - Persistent Lower Back Pain most common - Trigeminal Neuralgia sudden severe facial pain - Cluster Headaches one side head around eye - Cancer pain - Phantom limb pain: pain felt amputated limb after stump completely healed # Referred Pain: - Referred Pain: pain sensation area removed distant point origin - supplied same segment spinal cord site injury - Can acute chronic - E.g. Brain Freeze (cold throat felt head because they both connect same spot spinal cord therefore felt way) # Neuropathic Pain - Neuropathic Pain - result trauma disease PNS CNS - Its often chronic - Increased sensitivity painful non painful stimuli - Burning, shooting, shocklike, tingling - Injured nerves show increased sensitivity excitability - **Peripheral neuropathic pain:** - Diabetic neuropathy (high sugar levels damage nerves) - **Central neuropathic pain:** - Caused lesion dysfunction brain spinal cord - Multiple sclerosis - Parkinson disease - Phantom limb pain # Neuroanatomy - **Afferent Pathways** - sensory neurons feeling goes brain - Stimuli gets shot afferent pathway PNS → “gate” dorsal spinal cord → ascend higher centers CNS - Afferent goes back - **Interpretive Centers** - Located brainstem, midbrain. Diencephalon, cerebral cortex - Our brain interprets tells body what do - **Efferent Pathways** - Motor neurons - Descend from interpretive centers → “gate” dorsal horn spinal cord → modulate pain - 4 types sensory receptors: heat, cold, touch, pain - Nerve responds only type - Nerve continuous form periphery brain - **Pattern Theory** - Skin fiber endings were mostly identical each type sensation created using uniquely coded impulse formed spatial temporal pattern involving frequency pattern nerve transmission - **Gate Control Theory** - Recognizes importance mind brain pain perception - Psychological basis complex phenomenon pain - Experience pain depends interplay between CNS PNS - This theory paved way research cognitive behavioral approaches achieve pain relief - Pain messages overridden other signals produced these treatments - Heat cold - Acupuncture - Physical therapy massage - Prayer - **Neuromatrix Theory** - Helps understand: - Cognitive effects pain - Phantom limb pain - Placebo effect # Innate Adaptive Immunity - **General Adaptive Syndrome (GAS):** - GAS: you can adapt stress only long - Alarm stage - Resistance adaptation stage - Exhaustion stage (allostatic overload) - Can lead stress related diseases conditions - Musculoskeletal: Tension headaches - Connective Tissue: Arthritis - Immune system: immunosuppression - GI: ulcer, IBS - Endocrine: diabetes - **Specificity Theory:** - Amount paint directly related amount tissue injury