Patho objectives

Cell Biology and Genetics

1) State the functions of a typical eukaryotic cell

  • Prokaryotes; No distinct nucleus (single, circular chromosome), Lack histones, organelles, smaller, Cyanobacteria, bacteria, and rickettsiae, SIMPLER!
  • Eukaryotes; COMPLEX cellular organization, Membrane-bound organelles, Well-defined nucleus with several chromosomes, Higher animals, plants, fungi, protozoa, and algae

2) Describe the structure and function of the nucleus

  • Nuclear envelope

  • Nucleolus

  • DNA

  • DNA replication, repair, and transcription

  • Histone proteins

  • PRIMARY FUNCTIONS

  • Cell division

  • Genetic information

3) Describe the structure and function of the plasma membrane

  • Controls the composition of a space or compartment they enclose

  • Structure

  • Caveolae

  • Lipids-gives cell its structure

  • Phospholipids, glycolipids, and cholesterol

  • Fluid mosaic model

  • Flexibility

  • Self-regulating

  • Impermeability to some substances

  • Fluidity is impacted by temperature, amount of cholesterol

4) Describe cellular receptors

  • Carbohydrates

  • Glycoproteins-intercellular recognition

  • Proteins

  • Integral, peripheral, transmembrane

  • Provides cell with its many functions

  • Functions; Receptors, Transport, Enzymes, Surface markers, Cell adhesion molecules (CAMs), Catalysts

5) Identify the three mechanisms that bind cells together

Cell adhesion molecules

Extracellular matrix; Secreted by the cell itself, Meshwork of fibrous proteins in gel substance, Produced by fibroblasts, Diffusion of water, nutrients, and wastes between blood and tissue cells

Comprised of: Collagen, Elastin, Fibronectin (THINK FRUIT JELLO)

 Specialized cell junction; Two main functions

  • Hold cells together

  • Small molecules pass from cell to cell (coordination)

  • Three types= of Junctional Complex

  • Desmosomes

  • Tight junctions-barriers to diffusion

  • Gap junctions-clusters of communicating tunnels

6) Describe the primary modes of chemical signaling

  • Chemical signaling

  • Paracrine

  • Autocrine

  • Hormonal

  • Neurohormonal

7) Describe cellular catabolism and the transfer of energy to accomplish other cellular processes

  • Catabolism=energy releasing process (from proteins, lipids, polysaccharides found in food)

  • Three phases

  • Digestion-Lg molecules breakdown into smaller subunits

  • Glycolysis and oxidation- the splitting of glucose

  • Kreb Cycle- Needs O2, Produces 36 ATP molecules

8) Differentiate between passive/active transport.

Passive transport = movement of water and small and/or uncharged molecules, No energy expended, Diffusion of small, uncharged solutes, Concentration gradient, Filtration, Hydrostatic pressure (BP), Osmosis Movement of water

Active transport- Types

  • AKA Active transport

  • Energy expended

1) Protein transport pumps

  • Na/K pump

2) Transport by vesicle formation

  • Endocytosis

Pinocytosis

Phagocytosis

  • Exocytosis

9) Differentiate between endocytosis/exocytosis

Endocytosis- When substances are brought into a cell and engulfed

Exocytosis- When substances are released out of the cell

10) Differentiate between phagocytosis/pinocytosis

Phagocytosis- When a cell engulfs or takes in a large particle

Pinocytosis- Taking in of a liquid using small vesicles

11) Describe the changes in the plasma membrane that result in an action potential.

  • Depolarization
  1. Cell membrane becomes more permeable to Na+
  2. Na+ moves inside of a cell
  3. Membrane potential goes from negative to 0

  • Threshold potential

  • When a cell has depolarized by 15-20 millivolts

Action potential

  • The rapid reversal of polarity results in action potential

  • Membrane potential goes from 0 to positive

  • Repolarization

  • Refractory period

  • Absolute- cannot respond to any other stimulus

  • Relative- stronger than N stimulus can evoke an action potential

12) Identify the phases of mitosis and cytokinesis

1)Mitosis= nuclear division

2)Cytokinesis= cytoplasmic division

  • Phases of Mitosis and Cytokinesis

  • Prophase- first appearance of chromosome

  • Metaphase-spindle fibers pull chromosomes to opposite sides of the cell

  • Anaphase-centromeres split and sister chromatids are pulled apart, cell has 92 chromosomes now

  • Telophase- new nuclear membrane is formed around each group of 46 chromosomes, resulting in two identical diploid cells

13) Describe the stimulation of cell proliferation by growth factors

  • AKA Cytokines:

  • Stimulatory chemical signals

  • Transmit signals within and between cells

  • Major role in the regulation of tissue growth/development

Altered Cellular and Tissue Biology

  1. Describe the cellular adaptations occurring in atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia. Identify the conditions under which each can occur.

Atrophy: decrease, shrinkage of cell size

Hypertrophy: increase in cell size -> size of organ

Hyperplasia: increase in number of cells; cellular division

Metaplasia: reversible replacement of a mature cell type by a different mature cell type; e.g smoker=bronchi

Dysplasia: changes in size, shape, and organization of mature cells

  1. Identify the mechanism of cellular injury from hypoxia and chemicals

Hypoxic injury

  • Ischemia

  • Anoxia (no O2)

  • Cellular responses:

  • Decrease in ATP causing failure of Na/K pump and sodium-calcium exchange (cellular swelling)

        Chemical injury

  • **carbon monoxide
  • Lead
  • Ethanol
  • Mercury
  • Social or street drugs
  1. Identify the major types of cellular necrosis and cite examples of the tissues involved in each type. Compare necrosis with apoptosis.

Apoptosis: programmed cell death. An active process in which cells self-destruct in normal and pathologic tissues. (organized, regulated manner)

Necrosis: sum of cellular changes after local cell death and the process of cellular autolysis; usually occurring after severe/sudden injury. (disorganized, unregulated manner)

Coagulative necrosis

  • Kidneys, heart, and adrenal glands
  • Protein denaturation
  • Results from severe ischemia

        Liquefactive necrosis

  • Results from ischemic injury to neurons and glial cells in the brain
  • Tissues become soft, liquefy, and segregate from healthy tissue
  • Often caused by staphylococci, streptococci

        Caseous necrosis

  • Tuberculous pulmonary infection
  • Combination of coagulative and liquefactive necrosis
  • Tissues resemble clumped cheese (soft and granular)

        Fat Necrosis

  • Breast, pancreas, and other abdominal organs
  • Action of lipases (break down fat cells)

        Gangrenous necrosis

  • Death of tissure from severe hypoxic injury

  • Dry vs. wet gangrene

  • Gas gangrene

  • Necrotic tissue invaded by organisms, foul-smelling gases are produced

  1. Describe the biology of aging; characterize frailty.

Aging - time-dependent loss of structure and function that proceeds slowly and in such small increments that it appears to be the result of the accumulation of small, imperceptible injuries (“wear and tear”)

Cellular aging

  • Atrophy, decreased function, and loss of cells

        Tissue and systemic aging

  • Progressive stiffness and rigidity
  • Sarcopenia

        Frailty

  • Wasting clinical syndrome; vulnerable to falls, functional decline, disability, disease and death
  1. Characterize somatic death and its manifestations.

        Death of an entire person

        Postmortem changes:

  • Algor mortis - reduction of body temp
  • Livor mortis - purple discoloration at pressure points - pooling blood
  • Rigor mortis - within 6 hrs/Myosin-actin relationship/no ATP/muscle stiffening

Fluids and Electrolytes

  1. Describe the different compartments for body fluids and identify the fluid distribution changes occurring with age

Total body water (TBW)- 60% of body weight in adults

  1. THREE SPACES

  2. Intracellular fluid (ICF)

1) Inside the cells

  • 2/3 of TBW
  • Extracellular fluid (ECF)

2) Intravascular fluid- plasma

3) Interstitial fluid- space between cells and outside the blood vessels

  • Lymph, synovial, intestinal, CSF, sweat, urine, pleural, peritoneal, pericardial, and intraocular fluids

Pediatrics

  • 75% to 80% of body weight

  • Susceptible to significant changes in body fluids

  • Dehydration in newborns

  • Aged

  • Decreased percent of total body water

  • Increase adipose and decrease muscle mass

  • Renal decline

  • Diminished thirst perception

  1. Describe the factors that affect water and electrolyte movement

Capillary hydrostatic pressure- facilitates the outward movement of water from the capillary to the interstitial space (higher in arteries) PUSHING OUT

Capillary (plasma) oncotic pressure- osmotically attracts water from the interstitial space back into the capillary (higher in veins) PULLING IN

  • Key concepts to understand:

  • Fluid and solute exchange between blood and cells takes place at the capillary level

  • Two major factors determine the movement of water across capillary walls

  • 1) Hydrostatic pressure

  • 2) Plasma oncotic pressure

  1. Identify the mechanisms causing edema

Accumulation of fluid within the interstitial spaces

 Causes:

  1. Increase in capillary hydrostatic pressure
  2. Decrease in plasma oncotic pressure
  3. Increases in capillary permeability

Localized vs. generalized, Pitting edema, “Third spacing”

  1. Define isotonic, hypertonic, and hypotonic water and solute alterations and imbalances

Isotonic alterations

  1. Total body water change with proportional electrolyte and water change (no change in concentration)
  2. Isotonic fluid loss-HYPOVOLEMIA
  3. Isotonic fluid excess-HYPERVOLEMIA

Hypertonic alterations

  • Hypernatremia
  1. Serum sodium >145 mEq/L
  2. Related to sodium gain or water loss

Hypertonic alterations (cont’d)

  1. Major Cause:

  2. Dehydration

  3. Manifestations:

  4. Hypovolemia

  5. Hypotension, tachycardia, weak pulses

  6. Marked water deficit

  7. Headache, thirst, dry skin and mucous membranes,  concentrated urine

Hypotonic alterations

  • Hyponatremia
  1. Serum sodium <135 mEq/L

Major Causes:

  1. Pure sodium loss
  2. Low intake of sodium
  3. Dilutional hyponatremia

Manifestations:

  1. Lethargy, confusion, decreased reflexes, seizures, and coma

  2. If leads to loss of ECF and hypovolemia, see hypotension, tachycardia, decreased urine output

  3. If from excess water, see weight gain, edema jugular vein distention

  4. Identify the major manifestations of abnormal levels of sodium and potassium

Potassium level >5.5 mEq/L

Hyperkalemia is rare because of efficient renal excretion (peaked T waves)

Caused by increased intake, shift of K+ from ICF into ECF, decreased renal excretion, insulin deficiency, or cell trauma

Mild

  1. Increased neuromuscular irritability

  2. Tingling of lips and fingers, restlessness, intestinal cramping, and diarrhea

Severe

  1. The cell is not able to repolarize, resulting in muscle weakness, loss of muscle tone

  2. Major cardiac effects-bradycardia to cardiac arrest

Hypokalemia

Potassium level

Causes: reduced intake of potassium, increased entry of potassium into cells, and increased loss of potassium

Manifestations (depend on rate and severity)

  1. Membrane hyperpolarization causes a decrease in neuromuscular excitability, skeletal muscle weakness, smooth muscle atony, and cardiac dysrhythmias

  2. Differentiate between metabolic/respiratory acidosis and metabolic/respiratory alkalosis

Normal arterial blood pH

  1. 7.35 to 7.45
  2. Obtained by arterial blood gas (ABG) sampling

Acidosis; Systemic increase in H+ concentration or decrease in bicarbonate

Alkalosis; Systemic decrease in H+ concentration or increase in bicarbonate

Normal CO2 is 35-45 mmHg

Alteration in CO2 is the CULPRIT

  1. Respiratory acidosis—elevation of pCO2  (arterial carbon dioxide pressure) as a result of ventilation depression

  2. pCO2 is >45mmHg

  3. pH is <7.35

  4. Respiratory alkalosis—decrease of pCO2 as a result of alveolar hyperventilation

  5. pCO2 is <35mmHg

  6. pH is > 7.45

Normal Bicarbonate (HCO3) is 22-26 mEq/L

Alterations in Bicarbonate is usually the CULPRIT

  1. Metabolic acidosis—loss of HCO3 –  (bicarbonate)or an increase in H+ production

  2. HCO3 is <22

  3. pH is <7.35

  4. Metabolic alkalosis—excess of HCO3–  or an extreme loss of metabolic acids

  5. HCO3 is >26

  6. pH is >7.45

Major difference in metabolic and respiratory is in metabolic BICARBONATE is the culprit. In respiratory CO2 is the culprit

  1. Identify body mechanisms to buffer excessive hydrogen ion/acid

Carbonic Acid-Bicarboante pair (Most important)

Operates in the lung and the kidney.

The greater the partial pressure of carbon dioxide, the more carbonic acid is formed.

Bicarbonate and carbonic acid can increase or decrease, but the ratio must be maintained

  • EXAMPLE:

  • If the amount of bicarbonate decreases, the pH decreases, causing a state of acidosis

  • The pH can be returned to normal if the amount of carbonic acid also decreases

  • This type of pH adjustment is referred to as compensation

  • The respiratory system compensates by increasing ventilation to expire carbon dioxide or by decreasing ventilation to retain carbon dioxide

  • The renal system compensates by producing acidic or alkaline urine

Sodium

  • Primary ECF cation

  • Normal plasma lab value is 135-145mEq/L

  • Regulates movement of water

  • Roles

  • Neuromuscular irritability, acid-base balance, and cellular chemical reactions and membrane transport

Potassium

  • Major intracellular cation

  • Normal plasma lab value 3.5-5 mEq/L

  • Concentration maintained by Na+/K+ pump

  • Essential for transmission and conduction of nerve impulses, normal cardiac rhythms, and skeletal and smooth muscle contraction