Cellular Metabolism, Protein Synthesis and Waste

Module 1: The Cell

• Oxidative metabolism produces 95% of ATP
• Oxidative metabolism produces 20 times more ATP compared to anaerobic metabolism
• The inability to produce ATP through oxidative phosphorylation can negatively impact homeostasis

Protein Synthesis

• Cells turn DNA code into protein product
• RNA molecule serves as the intermediate in the process

Transcription

• DNA code transforms into RNA code and produces mRNA
• mRNA is single-stranded and transports a gene's genetic code out of the nucleus and into the cytoplasm

Translation

• mRNA attaches to ribosomes on the rough ER
• Transfer RNA (tRNA) transports amino acids to ribosomes to build protein
• Once built, the mRNA detaches and protein is released

Transportation

• Finished protein is secreted into a transport molecule
• Travels to the Golgi Apparatus (GA) for modification
• GA releases it into a secretory vesicle, which carries it to the cell surface for release

Waste Removal

• Lysosomes and peroxisomes are membrane-bound organelles that perform essential cleanup
• Serious diseases can arise if the function of either is compromised

Peroxisomes

• Detoxify molecules, contain catalase and oxidases
• Act on free radicals, especially hydrogen peroxide
• Oval or irregular in structure

Lysosomes

• Lysosomes handle larger components
• Eliminate senescent organelles, bacteria, and autodigest cells after death
• Contain numerous digestive enzymes and have a low pH
• Start small, growing by fusing to other vesicles

Cellular Transport

• Endocytosis involves vesicle formation around substances too large to pass directly
• Exocytosis involves vesicle formation to move substances too large to pass directly, out of a cell
• Pinocytosis is endocytosis specifically for fluids

Reversible Adaptations

• Atrophy involves cells shrinking but staying alive
• Hypertrophy means cells get bigger, but the number of cells remains constant
• Hyperplasia involves an increase in the number of cells

Metaplasia

• Metaplasia is a change in cell morphology
• One type of tissue transforms into another tissue type
• An example is glandular metaplasia in Barrett's esophagus
• In response to acid reflux, squamous cells of the esophagus transform into glandular cells similar to the small intestinal mucosa to withstand acidity
• Dysplasia is a pathological change and NOT an adaptive alteration
• Dysplasia is an early stage of neoplasia

Neoplasia

• Neoplasia involves abnormal cellular replication, tissue growth, and lifespan, potentially leading to tumors, malignancies, and cancers

Cellular Injury Causes

• Hypoxia (lack of oxygen) stemming from ischemia (lack of blood flow)
• Chemical agents such as drugs and alcohol
• Physical agents like trauma and heat
• Infections
• Psychosocial stressors or psychological trauma
• Genetic or nutritional defects
• Aging

Biochemical Response to Cellular Injury

• Response involves ROS/free radicals, which are chemically unstable and readily react with other molecules, resulting in chemical damage
• Damage can be created by ionizing radiation (X-ray, UV), redox reactions in mitochondrial electron transport and peroxisomes, and the metabolism of exogenous substances
• Low Reactive Oxygen Species (ROS) levels lead to immunosuppression
• Regular ROS levels lead to homeostasis and high ROS levels lead to autoimmunity
• The body has enzymes that neutralize free radicals
• If free radicals are not neutralized, lipid peroxidation, protein modifications and DNA fragmentation cause cell injury

Apoptosis vs. Necrosis

• Two different ways cells die, orderly or disorderly

Necrosis (Disorderly way)

• Cell size swells up and bursts
• Nuclear structure undergoes disorderly breakdown
• The cell membrane bursts
• No energy is required
• Cellular contents leak out of the cell
• Adjacent inflammation occurs
• Never physiological, meaning cells have been injured and cannot repair in an orderly fashion

Apoptosis (Orderly way)

• Cell size shrivels up and blebs
• Nuclear structure undergoes orderly fragmentation and digestion
• The cell membrane remains intact
• Energy is required
• Cellular contents are packaged into apoptotic bodies for digestion
• No adjacent inflammation occurs
• Usually physiological, meaning cells must turn over in the body

Neoplasia

• Very general understanding of the hallmarks of cancer (malignant neoplasms)

Self-Sufficiency in Growth Signals

• Normal cells use the RAS pathway to signal cellular growth
• The RAS pathway is interrupted by GAP and PTEN, made by tumor suppressor genes
• Mutations in oncogenes or tumor suppressor genes lead to excessive cellular proliferation

Insensitivity to Growth Inhibition

• p53: Tumor suppressor gene known as “Guardian of the genome"
• Provides surveillance on cell's genetic material and directs cell how to handle genetic damage
• Mutated p53 has unchecked expansions and leads to more mutations
• No surveillance, no DNA repair, no growth inhibition, and no senescence

Altered Cellular Metabolism

• Cancer cells use anaerobic glycolysis for carbon, helping them reproduce rapidly
• Lactate (waste product) builds up and is then used by cancer cells to harvest carbon

Evasion of Apoptosis AND Immortality

• Telomeres protect chromosomes from fraying or getting damaged
• When telomeres are degraded or used up, the cell recognizes that the DNA is now vulnerable to damage, which results in cell stopping reproduction and undergoing apoptosis
• Telomerase is an enzyme that tells telomeres to regenerate
• Tumors activate telomerase, even when the DNA is damaged or mutated, causing the cell to keep dividing
• The cell never receives a signal to stop reproducing or undergo apoptosis

Sustained Angiogenesis

• Vascular stimulators: VEGF and bFGF
• Pro-vascular endothelial signalers and increased blood supply to the tumor

Ability to Invade and Metastasize

• The ability to refer to how cancers spread

Ability to Evade Human Immune Response - 3 ways to evade immune system

• Don't display antigen on its MHC I receptor
• Stop making MHC I receptors
• Make immunosuppressive cytokines that kill T cells

Benign vs malignant – Neoplasm characteristics

• Benign neoplasms are defined as "-oma"
• Malignant neoplasms include adenocarcinoma, squamous cell carcinoma, leukemia, and lymphoma

Benign

• The cells and architecture are similar to normal tissue which provides differentiation
• Rate of growth is usually slow
• Local invasion usually pushes on but does not invade surrounding tissue
• No metastasis

Malignant

• The cells and/or architecture lack the differentiation of normal
• Rate of growth can be slow or fast
• Local invasion usually invades the surrounding tissue
• Frequent metastasis

How Cancers Spread (Three ways)

• Seeding of adjacent surfaces; for example ovarian cancer cells detach from the tumor then attach and grow as colonies on abdominal organs
• Lymphatic spread; for example breast cancer spread to axillary nodes
• Hematogenous spread; where cancer cells spread through the bloodstream

Fluid Regulation

• Common disruptions of electrolytes and how they present clinically

Sodium Imbalances

• Hypernatremia results in thirst, confusion, neuromuscular excitability, seizures and coma
• Hyponatremia results in a headache, confusion, stupor and seizures with a headache confusion, stupor, seizures, coma

Potassium Imbalances

• Hyperkalemia results in progressive muscle weakness (flacid paralysis) and cardiac issues.
• Hypokalemia results in spastic paralysis fatigue, cramps and fatigue, cramps, cardiac issues

Calcium Imbalances

• Hypercalcemia is coupled with cognition changes, confusion, coma, muscle weakness, arrhythmias
• Hypocalcemia is coupled with irritability, anxiety, paresthesia, bronchospasms, heart failure and muscle cramps

Starling's Forces

• Capillary hydrostatic pressure is the pressure exerted by blood against capillary walls, leading to filtration out of capillaries
• Capillary oncotic pressure is the osmotic pressure generated by proteins in blood, leading to reabsorption into capillaries

Edema Formation

• Edema can result from imbalances of filtration and reabsorption
• Edema is a build-up of fluid
• In the interstitial space, edema occurs when hydrostatic pressure > oncotic pressure
• The Lymph system picks up excess fluid from tissues to put back into the blood (too much fluid creates edema)
• Or edema occurs when oncotic pressure < hydrostatic pressure

RAAS (Renin-Angiotensin-Aldosterone System)

• ↓blood flow to kidneys, ↓BP, ↓extracellular fluid levels (↓blood volume), ↓sodium levels in blood, ↑sodium levels in urine causes the kidney releases renin
• Renin pairs with angiotensin that's released by the liver, converts angiotensinogen into angiotensin I
• Angiotensin converting enzyme (ACE) from the lungs converts angiotensin I into angiotensin II

Two roles of angiotensin II

• Constricts the arterioles (vasoconstriction) → ↑ BP
• Goes to the adrenal cortex in the kidney → Adrenal cortex makes aldosterone → Aldosterone tells the kidney to not let sodium or water leave the body into urine
  • Sodium and water are put back into bloodstream which causes blood volume to ↑ and BP to ↑
• If RAAS goes into overdrive → Hypertension

ADH

• Secreted by posterior pituitary (within hypothalamus) in response in blood osmolality (dehydration)
• Results in production of more concentrated urine to reduce loss of fluid from urination
• Compared to RAAS that results in both water and sodium retention, ADH results only in water retention
• Allows circulating volume to be better maintained until more fluids can be consumed

Types of Imbalances in Acid/Base balance

Metabolic Acidosis

• Excessive buildup of acid (H+ ions) OR excessive loss of bicarbonate

Metabolic Alkalosis

• Loss of acid from blood resulting in an excess of bicarbonate
• Causes excessive vomiting, hyperaldosteronism, diuretics

Respiratory Acidosis

• Excessive build-up of CO2

Respiratory Alkalosis

• Excessive loss of CO2
• Causes Hypoventilation (due to the use of, medications, drugs, or CNS depression), diffusion issues, or obstructive lung disease
• Causes hyperventilation (due to altitude sickness and panic attacks)

pH: 7.35-7.45 HCO3: 20 - 24 mEq/L CO2: 35 - 45 mmHg Na: 135 - 145 - mEq/L K: 4 mEq/L CI: 100 mEq/L

Importance of the Anion Gap

• Anion gap determines the underlying cause for metabolic acidosis
• Anion gap = Difference in cation and anion ratios in plasma (lab result from blood arterial gases (ABG) test)
• Normal anion gap ~12 mmol/L → Too little or loss of bicarbonate
  • Chronic diarrhea
  • Pancreatic issues
  • Renal tube acidosis Elevated anion gap → Excessive build-up of acid
  • Lactic acidosis
  • Ketoacidosis
  • Other renal failures
  • Medications
  • Inherited metabolic disorders

Components of Blood

• Plasma vs. serum includes both coming from the liquid portions of blood once cells are removed

Serum

• Liquid that remains after blood has clotted
• There is no fibrinogen because it has been used up

Plasma

• Liquid that remains when clotting is prevented w/ addition of an anticoagulant
• It still has fibrinogen

Plasma Proteins

• Most are made in the liver
• Exception: Immunoglobulins (Ig) – Functions in defense and are made by plasma cells in lymph tissue
• Most abundant is albumin, which aids maintenance of oncotic pressure
• They have functions of:
  • Fibrinogen (clotting)
  • Transferrin and albumin (transport)
  • Cytokines (Regulation and include hormones and chemicals that regulate various body functions, primarily immune)

Myeloid vs. Lymphoid Cell Lines

• Stem cells can differentiate along the myeloid or lymphoid cell line, directed by cytokines and growth factors

Myeloid Line

• RBC's, WBC's (except lymphocytes), platelets
• GM-CSF (Colony stimulating factor) leads to the myeloid cell differentiating into any of these cells, when it's present
  • Growth factors or cytokines stimulate further specificity
    • Granulocyte progenitors makes cells that have granules in them (monocytes and neutrophils)
    • Megakaryocyte gives rise to platelets
    • Proerythroblast differentiates into mature RBC in presence of hormone erythropoietin (EPO), produced by the kidneys

Lymphoid Line

• Immune cells (lymphocytes: B cells and T cells)
  • B cells differentiate into plasma cells that produce antibodies
  • Pro-T cells differentiate into cytotoxic CD8+ T cells and helper C4+ T cells

Role of EPO

• Hemoglobin is where it's made, what's needed to make it, how it's recycled, and its function
• EPO promotes formation of hemoglobin (in RBCs) in the bone marrow
• Hemoglobin (Hgb) is a protein that gives RBCs O2 carrying capacity

Composition of HgB

- 4 heme rings, each ring has an iron atom that carries O2
- 1 Hgb is made up of 4 chains, 2 alpha chains and 2 beta chains. And 1 heme in each of these chains
- 1 HgB carries 4 O2 molecules

Nutrients needed to make Heme components

    - Needs vitamin C to keep iron in a +2 state
    - Needs copper to bring it from the tissues to the bone marrow to make RBCs
    - B6 (pyridoxine) and pantothenic acid and Folate, B12, B2, and protein

Heme Ring

- B6 (pyridoxine) and pantothenic acid

Cells

- Folate, B12, B2, and protein

Heme Recycling

• Lifespan of a RBC is 120 days
• RBCs return to the spleen to die:
  • Macrophages eat them and dispose of toxic components
  • Heme comes off of dying RBC and breaks down into heme ring & iron
  • Heme ring is carried on albumin as bilirubin. It's then taken to the liver where it's converted to urobilinogen
  • Can leave the body via kidney or stool (GI tract) OR be recycled through entero-hepatic circulation (GI-Liver) Iron is taken by transferrin, secreted w/ bile by the liver, taken to liver then to bone marrow to make more RBCs, stored and released in the spleen to make more RBCs, and taken directly to the bone marrow for more heme synthesis

Oxygen-Hemoglobin Dissociation Curve (Left vs. Right shift)

Left Shift

• (Love for Lungs), oxygen will stay with or go to hemoglobin in cases of Alkalosis, low temp, or low partial pressure of CO2
• Hgb has higher affinity for O2 in these cases and wants O2 to go to it and stay with it
• Lungs meet this set-up, so Hgb picks up O2 easily here

Right Shift

• (Running with tissues), O2 will leave Hgb and go to the tissues in cases of Acidosis (lactic acid, when CO is being given off) high temp, or elevated 2, 3 DPG (part of glycolysis pathway)
• Hgb has lower affinity for O2 in these cases
• The test wants O2 to leave it and go to the tissues

Significance of a Shift in Hemoglobin's Affinity for Oxygen

• Oxygen Saturation and Oxygen Availability

Left Shift

• There's greater affinity for O2
  • Higher oxygen saturation and decreased oxygen availability to tissues

Right Shift

• There's less affinity for O2
  • Lower oxygen saturation and increased oxygen availability to tissues
  • Anemia with 3 main classifications and common causes

Anemia

• Three main classifications of anemia and common causes

Normocytic, normochromic ( Normal cells, normal color)

• Low RBC production or a high RBC production can cause anemia
  • Low production can be traced to a deficiency of bone marrow, bone marrow mass crowding, and leukemia eventing production and chronic disease
    • Chronic inflammation leads to cytokines and cellular destruction to down regulation of RBC production
    • Hemorrhaging can hemolize the blood causing (RMB's losing integrity and breaking apart) and malignancy (cancer)

Hemorrhaging

• Small cells, low color, not enough heme (pale)
• Defects in homeostasis

Microcytic

• Defects in homeostasis
• Long term issues with the bone marrow

Macrocytic

Macrocytic, normochromic (Big cells, normal color)

• Problems in hemastasis
• Folate deficiency can occur

Normocytic, normochromic

- RBC: Low
- Hgb: Low
- Hct: Low 

Microcytic, hypochromic

- MCV: Low
- MCH: Low
- H+ ions: low

Macrocytic, normochromic

- MCV: High
- MCH: Normal

Sickle Cell Anemia

• Autosomal recessive disease
• Severely depends on what part of the Hgb becomes damaged
• Bilateral pain that can cause swelling in other parts of the infected cells
• Difficulty breathing and decreased 02 intake

Hemophilia

• Genetic disorders leads to easy bruising or bleeding
  • More common in females
• Factor 8 or 9 is a big problem that causes hemophilia

  Role of Platelets

  • Regulate blood flow/ damages the veins
  • Allows for the plugging of the veins to cause bleeding
    • Starts the clotting processes including breakdown

Clotting

• Where clotting factors are made
  • Liver
• How clotting
  • Vitamin K is essential

Lab tests

• Measuring to where's the plasma levels are after forming a clot
• Showing their is a mature cot that will be broken down eventually (DE dimer test)

PT test(Prothombin testing)

PTT test ( same as PT but goes plus to 8+)

• Looking at the blood to see if hemophiliac is occurring

Modules 3

• General knowledge of wbC's and other involved and non involved to help stop immunity

Inmate Immunity

Mast cells

• Physical agents and or microbes
• Causes the immune and system to start

Monocytes

• Surrounds the infected tissues

Neutrophils

• Is the fist respond and the infection

Dendritic cells

• To communicate the adaptive immunity

T-cells

• Kill infected cells in the body

Natural killer cells

• Cytotoxic lymphocytes that have programmed the cell is not to be killed, however can be fixed

The cells that don't

• The infected cell is not to release more contents Cytokines
• Mediator in inflammation that help and assist Interleukins
• Protect those cells from causing more inflammation
• Type 1 help alerts they body from getting infected

Clotting factors

• Helps in the aid for the body with protein and plasma

Complimentary

Bradykinin

• Proteins that helps to wait and activate

Acquired Immunities

• Third line defence for immunity after the virus enters the body Antigen is a antibody with a immune system

LYMPHODIES

-The centre cell for adaptive acquired immunity Cell mediated immunity

• T-cells and NK cells Humoral immunity
• cells to help with antibody production and release Antibiotics
• Released by those be cells to help protect extra cellular pathogens

Module 4

Dyspnea

• Common symptom of being over weight and not being able to get enough oxygen

pNeumothorOx

• Air inside of the lungs/chest
• Types such as traumatic (shot or stabbed in the lung) Tension (life threatening to patients)
• High blood pressure

pLeural effusion

• Too much access fluid inside to lungs and need to have extra care and assistance

Brochiolitis

• Not enough fluids to allow airflow for children

Epiglottis

• Swelling of the throutes
• In most cases people pass
• Can cause pain and other infection problems

Pumonary edema

• Too much fluids inside the lungs Causes the person to suffocate from fluid. High white cell counts

Pulmorany embolism

• Cause chest pain and and fatigue due shortness of breath Virchow's triad Risk from people who has heart blood clot Increased blood flow that leads to clotting (blood vessels don't have blood flow)

Pneumonia

• Viral and bacteria can cause Risk is 65 yr to 2 year old's old being smokers or unvaccinated
• Fevers sweating for chills

Contagious issues with infection and lungs that caused droplets Mybactericun caused problems with antibacterial medicine

all/ards

• Acute inflammation caused by traimua or infection
• High cause of death from cells from the outside to the inside of the cells

Sypmtins

• Hypoxaemia
• High blood pressure and low blood pressure

Asthma

• Chroinc diseases that makes people suffer and and or causes death with infection

COPD and CHRONIC BRONCHITIS

• Impairment and lungs are destroyed Rare genetic deficienys issues

Module 5 Too learn normal anatomy and physiology and past content

Renal/kidney

• Regulated by blood
• Ph balance for the body by excreting other materials

Labs that do aid kidneys

Test by urine to that chemicals that can change to the color if needed

A-K-i is cause by infections damage by glomerulus

• Autoimmune condition and strep throat in the body to help treat

tubal-necrosis

• Blood caused infection on both sides of the body Caused by sepsis and high blood pressure.
• High electrolyte imbalances which can lead to even higher problems and problems

Pre- renal

• High kidney preasure and lack of blood to cause infection to all body organs

60th cards

• Too much stress and pain for that can cause the body to turn upside to down

Ckd can be staged

• Based on high stress high pressure

Module 6

• A basic understanding of the human anatomy

Loop of Henle

• To control the amount of volumes are need to make a new body

A D h

• Is more control the amount of h2o and fluids level in the areas

Loop diuretics

• Medications that provide the infection level of Furosemide Block Reabsorption of the loops.