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Advanced Pathophysiology
Basic Cellular Functions -
- Movement
- Conductivity
- Excretion
- Metabolic Absoption
- Creation of ATP
- Tissue Growth
- Communication
- Secretion Functions of Plasma Membrane -
- Structure
- Protection
- Activation of Cell
- Transport
- Cell to Cell Interaction Nucleus Function - Membrane bound structure, controls cell division and contains genetic information/material Cytoplasm - Cytoplasmic matrix that surrounds organelles Mitochondria - Primary energy maker, responsible for cellular respiration & energy production, makes ATP Smooth Endoplasmic Reticulum - An endomembrane system where lipids are synthesized, calcium levels are regulated, and toxic substances are broken down. Rough Endoplasmic Reticulum - An endomembrane system covered with ribosomes where many proteins for transport are assembled. Golgi apparatus - A system of membranes that modifies and packages proteins for export by the cell Lysosomes - originate in Golgi, 40 digestive/degradative enzymes that catalyze proteins,
lipids, nucleic acids, carbs Peroxisomes - Contain oxidative enzymes that detoxify compounds and fatty acids and breakdown substances into harmless products Cytoskeleton - A network of fibers that holds the cell together, helps the cell to keep its shape, and aids in movement Vesicles - small membrane sacs that specialize in moving products into, out of, and within a cell Vacuole - Cell organelle that stores materials such as water, salts, proteins, and carbohydrates Ribosomes - RNA protein complex that is responsible for protein synthesis (free & attached) Cell membrane (plasma membrane) - phospholipid bilayer that surrounds all cells and regulates what enters and leaves the cell Muscle Cells Function -
- Can be striated (skeletal) or smooth (bowels, bronchi)
- Can generate forces that produce motion
- Can be smooth AND striated (diaphragm or intercostals) Cardiac & Neuro Cells Function -
- Stimulus causes excitation & electrical potential that passes along surface of cell to reach destination
- Cardiac muscle cells have automaticity GI & Kidney Cells -
- All cells take in nutrients but cells of intestines & kidneys specialize in absorption
- Kidney tubules reabsorb fluids and synthesize proteins
- Intestinal epithelial cells reabsorb fluid & synthesize protein enzymes Endocrine & Neuro Cells -
Filtration - Filtration is movement of water and solute molecules across the cell membrane due to hydrostatic pressure generated by the cardiovascular system. Hydrostatic Pressure - hydrostatic pressure in blood vessels is the pressure of the blood against the wall. It is the opposing force to oncotic pressure. Tonicity - solute can exert a certain amount of pressure referred to as tonicity. This pressure can affect the fluid volume and the pressure in a cell by affecting the movement of water down its concentration gradient. Passive Transport - Movement of ions and other atomic or molecular substances across cell membranes without need of energy input. Types of Passive Transport -
- Simple Diffusion
- Facilitated Diffusion
- Filtration
- Osmosis Facilitated Diffusion - Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembrane integral proteins. Moves with concentration gradient Active Transport - Active transport is the movement of a substance across a membrane against its concentration gradient. Requires ATP Exocytosis - a process by which the contents of a cell vacuole are released to the exterior through fusion of the vacuole membrane with the cell membrane. Endocytosis - The taking in of matter by a living cell by invagination of its membrane to form a vacuole. Action Potential - An action potential (AP) is the mode through which a neuron transports electrical signals. It is defined as a brief change in the voltage across the membrane due to the flow of certain ions into and out of the neuron. Depolarization - The process during the action potential when sodium is rushing into the cell causing the interior to become more positive.
Depolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell. Repolarization - Period during which potassium ions diffuse out of the neuron. Repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential has changed the membrane potential to a positive value. Hyperpolarization - It inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold. •Less Excitable Hypopolorization - Smaller than normal stimulus could reach threshold potential and depolarize the cell. •More Excitable Does Low Potassium Cause Cell to be MORE or LESS Excitable? Why? - Causes cell to be less Excitable, potassium (K+) is positivity charged. Having less potassium makes cell more negative or Hyperpolarized, requiring more stimulus to generate an action potential. Does high potassium cause cell to be MORE or LESS excitable? Why? - Causes cell to be more excitable, potassium (K+) is positively charged and causes testing membrane potential to become less negatively charged requiring less than normal stimulus to generate an action potential. 5 Ways Cells Communicate -
- Contact Dependent
- Autocrine
- Paracrine
- Synaptic
- Endocrine Tight Junctions - Tight junctions, also known as occluding junctions or zonulae occludentes (singular, zonula occludens) are multiprotein junctional complexes whose general function is to prevent leakage of transported solutes and water and seals the paracellular pathway. Gap Junctions - Gap junctions are a specialized intercellular connection between a multitude of animal cell- types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulated gate between cells. Desmosomes -
- Change in size, shape or organization, abnormal development of cells.
- May be reversible, may lead to malignancy
- IT IS NEVER NORMAL
- Ex. Epithelial, cervical Metaplasia -
- Reversible replacement of one mature cell by another differentiated cell type
- Bronchial columnar cells by squamous cells (recurrent injury)
- Squamous cells do not secrete mucus or have cilia thus loosing vital protective mechanism Aquaporins - Aquaporins, also called water channels, are integral membrane proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. Net Filtration -
- Is a calculation of the forces that favor filtration vs the forces that oppose filtration Fluid distribution between the permeable capillaries of the vascular and interstitial bed is going to be the net result of oncotic pressure and hydrostatic pressure—measurements of these forces pulling and pushing against each other
- Pushing and pulling of fluid will determine if fluid moves out of capillary and into interstitial space=filtration. Or if fluid moves into the venous end of the capillary=reabsorption Examples That Cause Edema -
- Liver failure resulting in portal hypertension causing fluid to leak out of capillaries. Also decreases the production of blood proteins such as albumin, decreasing osmotic pressure in vessels.
- Hypertension leading to increased hydrostatic pressure filtering more fluid into interstitial space.
- Increase in blood vessel permeability due infection or injury or burn causing increased fluid to accumulate in interstitial space.
- Increased venous pressure and decreased reabsorption and thus increased hydrostatic pressure due to heart failure.
- Lymphatic obstruction decreasing absorption of fluid into lymphatic system. Oncotic Pressure (Colloid Osmotic Pressure) - Pressure exerted by plasma proteins that pull fluid back into blood vessel. Or into interstitial space. Remember RAAS System and Function -
Natriuretics - ANP, BNP, Urodilatin - Does opposite of RAAS System. Responds to increase volume in vessels. Antidiuretic Hormone (ADH) - ADH is also called arginine vasopressin. It's a hormone made by the hypothalamus in the brain and stored in the posterior pituitary gland. It tells your kidneys how much water to reabsorb in distal renal tubules. ADH constantly regulates and balances the amount of water in your blood. Released in response to increased blood osmolality or decreased blood volume. Isotonic Fluid loss (Isotonic Dehydration) - Water and sodium are lost in equal proportions. Vomiting and diarrhea are most common especially in Gastroenteritis. Excessive sweating may also cause. Hemorrhage, wound draining and decreased fluid intake. Isotonic Fluid Loss Exam Findings - Weight loss, Dry Mucus Membranes, Skin Turgor (Tenting), Hypovolemia, Oliguria, Increased Urine Specific Gravity, Elevated Liver Enzymes and Pancreatic Enzymes. Hypertonic Dehydration (Hypernatremia) - Water excretion from body exceeds that of sodium excretion. Blood somolality increases causing water to shift from intracellular to extracellular space. Causes of Hypernatremia - Fever (Increases respiratory rate losing water, sweating, decreased fluid intake), Polyuria (Diabetes mellitus, Insipidus, and diuretic use), End-Stage Renal Disease (Tubal dysfunction and Free water clearance dysfunction. Hypernatremic Exam Findings - Intracellular dehydration, convulsions, pulmonary edema, hypotension, tachycardia, increased serum osmolality, increased serum sodium, decreased urine output (Unless caused by polyuria or diuretics), increased urine specific gravity. Hypotonic Dehydration (Hyponatremia) - Sodium Loss is Greater than water loss. Decreases serum osmolality, shifts water from extracellular to intracellular. *Hyponatremia most commonly caused by water excess and/or retention rather than sodium loss. Causes of Hyponatremia - Addison's Disease (Adrenal insufficiency, decreased cortisol and aldosterone production), Renal tubular acidosis, Diuretics (Loop, Thiazides and Osmotic Diuretics), Cystic Fibrosis (defective Chloride Ion Transport resulting in excessive sodium loss in sweat.) Excess water intake or IV fluid intake. SIADH, Cirrhosis, CHF (Increased AVP and compensatory response). Hyponatremia Exam Findings - Decreased sodium level, decreased serum osmolality, cerebral edema, decreased urine specific gravity, headache, nausea, lethargy, confusion, coma, death.
E-xcessive Urination Hypercalcemia Causes - 90% attributed to Hyperparathyroidism and Cancers. Other causes - Vitamin D and dietary calcium excess, hyperthyroidism, paget's disease, thiazide use. Hypophoshphatemia Causes - Intestinal malabsorption Increased renal excretion Hyperparathyroidism malnutrion, Vit D, deficiency, alcoholism, severe burns, DKA, Fanconi Syndrome, X-linked familial hypophosphatemia Hypophosphatemia S/S - Paresthesias, Muscle weakness, Muscle pain, Mental changes, Cardiomyopathy, Respiratory failure, increased serum calcium. Hyperphosphatemia Causes - Hypoparathyroidism, High Vit D, DKA, muscle damage, infections, acute and chronic renal failure, treatment with chemotherapy (releases large amounts of phosphate into serum), laxative and enema use containing phosphates. Hyperphosphatemia S/S - Neuromuscular irritability Muscle weakness Hyperactive reflexes Tetany Positive Chvostek's or Trousseau's sign Hypermagnesemia Causes - Most commonly caused by Renal or Kidney failure. Lithium therapy Hypothyroidism Addison's Disease Milk-Alkali Syndrome (high calcium and metabolic acidosis from excess calcium and alkali supplements for osteoporosis and antacids) Drugs containing magnesium Hypermagnesemia S/S - Weakness and Nausea Impaired Breathing Hypoventilation Hypotension Low Serum Calcium Arrhythmias and asystole Decreased or absent deep tendon reflexes Dizziness Sleepiness
Hypomagnesemia Causes - Most common are decreased GI absorption and increased renal loss. Alcoholism, CHF, DM, chronic diarrhea, Hypokalemia, Hypocalcemia, Malnutrition, celiac disease. Hypomagnesemia S/S - Nerumuscular and neuropsychiatric disturbances, hyperexcitability, tremor, tetany, convulsions, muscle cramps, weakness, vomiting. Causes for Acidosis - Lung Impairment - COPD, Pneumonia, lung diseases or traumas. Diarrhea, DKA, Renal failure, Drug Overdose. Protein Buffer System - Hemoglobin serves as buffer. Hemoglobin = Amino Acid which has NH3+ _C_COO-, H+ can bind to COO- if blood is acidic, or release the H+ if blood is alkalinic. NH3+ can drop a H+ if blood is alkalinic or bind a H+ if blood is acidic. Approx 250 million Hemoglobin in every RBC. Causes of Alkolosis - Hyperventilation, vomiting, increased H+ loss from diuretics, high altitudes, hyper-metabolic states such as fever. Bicarbonate Buffer System - a solution of carbonic acid and bicarbonate ions, regulated by lungs by blowing off CO2 and Kidneys by releasing Bicarbonate and/or excreting H+ Phosphate Buffer System - Buffers ICF and Urine. Consists of Dihydrogen phosphate ions and Hydrogen Phosphate ions. Dihydrogen Phosphate can release an H+ increasing acidity and Hydrogen Phosphate ions can bind H+ to increase alkalinity. Ammonia Buffer System - Ammonium is generated in tubular cells through glutamine metabolism. Ammonia binds to protons and helps kidneys when maximum proton absorption by tubules are reached. DNA Structure - DNA consists of two long chains of nucleotides twisted into a double helix and joined by hydrogen bonds between the complementary bases adenine and thymine or cytosine and guanine DNA Function - Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living things. All known cellular life and some viruses contain DNA. The main role of DNA in the cell is the long-term storage of information. What is considered the backbone of DNA -
Protein then goes through folding into a more stable structure to create specific proteins. How many chromosomes does a Somatic Cell have? - 46 Chromosomes (23 Pairs) Which cells do not contain DNA? - Mature red blood cells, cells in hair and nails. Gametes consist of which cells? - Sperm and Egg Cells Contain 23 haploid cells, or chromosomes.
