Patho Pharm Unit 1

Etiology

cause of disease

Monogenic

One gene

Polygenic

Multiple genes

Idiopathic

No known cause

Multifactorial

Genes + Environment

Nasocomial

Acquired within the health care environment

Iatrogenic

Acquired during medical treatments or procedures

Disease

Functional impairment of cells, tissues, organs, and/or organ systems

Genetic Disease

Caused by abnormalities in an individuals DNA which can be inhereted or a result of mutation

Congenital Disease

Disease present at birth, which may be caused by genetic factors, environmental or both

Acquired Disease

disease that develops after birth due to environmental factors, infections, lifestyle choices, or other external influences

Pathogenesis

Development and progression of the disease within the body

Type 2 Diabetes Etiology

Caused by insulin resistance and several related factors

Type 2 Diabetes Pathogenesis

Insulin resistance leads to high blood sugar levels because glucose cannot effectively enter cells

Sign

Objective observations (blood in stool, skin rash)

Symptom

Subjective - patient “says” (back pain, stomachache)

Asymptomatic

No symptoms (screenings imperative)

Acute

sudden onset

Chronic

persistent or ongoing

Local

specific region or area of body

Systemic

Entire body or multi-organ or system

Remissions

symptoms improve or temporarily disappear

Exacerbations

symptoms worsen or flare up

Plasma membrane

• Selectively permeable

• provides protection and regulates movement of substances in and out of cell

Cytoskeleton

network of protein and tubules that provides structural support from within. Maintains cell shape and facilitates movement

Phospholipid Head

Hydrophilic - faces outward to the aqueous environment

Phospholipid Tail

Hydrophobic - faces inward away from water

Simple diffusion

No protein or energy needed

Facilitated diffusion

Protein needed, no energy

Primary Active Transport

Energy and Protein needed

Ligand

Opens protein - drugs can mimic its effect

Mitochondria Functions

- ATP (krebs, ETC)

- Apoptosis

- Thermogenesis (in brown adipose tissue) keeps us warm

Anaerobic

Glycolysis only (lactic acid produced)

Membrane potential

resting, depolarization, repolarization

Oxygen is necessary for the

Electron Transport Chain

Na+ / K+ pump

3 Na+ out, 2 K+ in

ER

network of membranes that plays a crucial role in producing, processing, and transporting lipids and proteins

Smooth Er

Lipid synthesis

Rough ER

Protein synthesis

Lipids

-fats, oils, phospholipids

-serve as major energy source and structural components of cell membranes and signaling molecules

-specific enzymes in smooth ER catalyze production

Proteins

-Made up of amino acids

-hemoglobin, insulin, enzymes, antibodies

-Complex structures and functions

-ribosomes transcribe mRNA into amino acid sequences and assemble them into protein

Hormones can be both

Lipids & Proteins

Atomic Organization

Cells → Tissues → Organs → Organ Systems

Tissue

group of cells that work together to perform a specific function or set of functions

Main types of tissues

epithelial, connective, muscle, nervous

Epithelial Tissue

covers body surfaces, lines cavities and organs, and forms glands (skin, digestive tract)

Connective tissue

Supports, protects and binds together other tissues and organs (bones, blood, adipose fat tissue)

Muscle Tissue

Facilitates movement by contracting (skeletal muscle, cardiac muscle, etc.)

Nervous tissue

Transmits electrical signals and processes info (brain, spinal cord, nerves)

Cellular adaptation

reversible response to physiologic and pathologic changes. Only temporarily successfully usually.

Atrophy

Reduction in cell size

Mechanism of atrophy

- Reducing the organelles and cytoplasmic components

- Breakdown of cellular structures and a decrease in metabolic activity

Examples of atrophy

-Muscle cells shrinking from disease

-Neurons shrinking due to neurodegenrative diseases

Impact of atrophy

Decline in the cells ability to perform its normal functions

Hypertrophy

Increase in cell size

Examples of hypertrophy

muscle cells enlarging from physical exercise

cardiac muscle increasing in size in response to high BP

Impact of Hypertrophy

can improve or disrupt normal function/strucutre, leading to dysfunctional tissue or organ performance

Mechanisms of Hypertrophy

- Augmenting organelles and cytoplasmic components

- Synthesis of more proteins and cellular components

Hyperplasia

Increase in cell number

Mechanism of Hyperlasia

Increased rate of cell division

Examples of hyperplasia

-growth of endometrium during menstrul cycle

-liver regeneraition

-Benign prostatic hyperplasia

Impact of hyperplasia

Usually maintains a normal organization and function and can help tissue adapt to increased demands, but can potentially lead to disease

Metaplasia

Transformation in cell type

Mechanism of Metaplasia

- Cells replace one cell type with another cell type

- Typically to cope with a stressor

Example of Metaplasia

Normal columnar epithelial cells replaced by squamous ones in response to chronic smoking

Impact of metaplasia

can be an adaptive response to chronic stress/injury, potentially protecting from further damage or progressing dysplasia

Dysplasia

abnormal development or growth of cells (non reversible in some cases)

Mechanism of Dysplasia

-cells exhibit irregularities in size shape and organization

-changes not yet malignant but are atypical

Example of dysplasia

Dysplastic cells in the cervix

Impact of Dysplasia

Often a precursor to cancer — presence can indicate an increased risk of developing malignancy if not monitored or treated

Cellular injury

Damage to cells that impairs their normal function and structure - leads to cell dysfunction or death if not resolved

4 types of cellular injury

Hypoxic injury, ischemia-reperfusion injury, oxidative stress, chemical injury

Hypoxic Injury

lack of oxygen

Most common cause of cellular injury

Hypoxic injury causes

reduced O2 supply

Circulatory problems

Hemoglobin dysfunction

Impact of hypoxic injury

Disrupts cell differentiation, angiogenesis, proliferation, erythropoiesis

prolonged hypoxia can lead to irreversible damage

Mechanism of Hypoxic Injury

- Less O2—> Decreased ATP

- Lactic acid accumulation from anaeroobic metabolism

- Disruption of Na+ / K+ —> influx of Na+ in cell —> swelling due to lack of ATP

- Inflammatory response !!

Ischemia-Reperfusion Injury

- Cells/tissues are reoxygenated after ischemia

- Causes are myocardial infarction, stroke, organ transplant

Impact of Ischemia-Reperfusion Injury

- Cell membrane damage

- Mitochondrial dysfunction

- Activation of cell death pathways (apoptosis or necrosis)

- Impaired organ function or tissue necrosis

Mechanism of Ischemia-Reperfusion

- Leads to production of Reactive Oxygen Species (ROS) & Free Radicals

- Cell membrane damage —> electrolyte imbalances —> cell death

- Increased intracellular Calcium —> damaged mitochondria —> decreased ATP

- Inflamattory Response!

What does Increased intracelular Calcium do

Damages mitochondria —> Decreased ATP production

Oxidative Stress

- Cell/tissue ROS exceed antioxidants (via pollution, radiation, etc.)

- Leads to damage of cellular components and trigger inflammatory response

Mechanism of Oxidative Stress

- Lipid peroxidation —> cell membrane damage

- Protein unfolding

- DNA damage

- Mitochondrial damage

Chemical/Toxic injury

- Cells/tissues are disrupted by harmful substances

-Caused by drugs, pollutants, industrial chemicals, and environmentl toxins

- Cells may attempt protein repair, or activation of repair pathways OR acute or severe exposure can overwhelm cellular defenses, leading to cell injury, dysfunction, or death

Mechanism of Chemical/Toxic injury

- Formation of ROS

- Converted into toxic forms within cell

- Damage to cellular structures like membranes, proteins, ion transport

- Interfere w/ energy production, protein synthesis, ion transport

-Liver and kidneys try to combat it temporarily

Common mechanisms of cellular injury

-ATP Depletion (Main problem)

-Increased ROS

-High intracellular calcium

-Mitochondrial damage

-Membrane damage

-protein misfolding

Apoptosis

Controlled cell death

Necrosis

Uncontrolled, accidental cell death —> inflammation & tissue damage (only good in small amounts)

Autophagy

Cellular process that involves the degradation and recycling of damaged or unnecessary cellular components to maintain cellular homeostasis an function — Neither good nor bad (self eating)

Two major roles of DNA

Replication and Proein Consruction

DNA Polymerase

Adds complementary bases and proofreads the strand to ensure appropriate basses are added

Interphase

period of the cell cycle between cell divisions

92

# of chromosomes in a cell right before division

Centromere

connects sister chromatids

Uracil

Nitrogen base that pairs with adenine in RNA

RNA polymerase

Binds to promoter region of DNA to make mRNA

Introns

Noncoding segments of nucleic acid that lie between coding sequences.

Transcription

DNA —> RNA

Translation

RNA —> protein

tRNA

type of RNA that carries amino acids to the ribosome

20

number of amino acids