Intro to Patho

Pathophysiology

The study of the functional changes that occur as a result of injury, disorder or disease

Disease

Syndrome, Illness, Injury

Pathogenesis and Etiology

• Risk Factors

• Pathogen

• Multifactorial

• Idiopathic

• Nosocomial

• Iatrogenic

Clinical Manifestations

• Local

• Systemic

• Acute

• Chronic

  • Insidious

  • Remissions/Exacerbations

• Subacute

Objective

signs

subjective

symptoms

Diagnosis

• definitive

• syndrome

• medical description

• prognosis

  • morbidity

  • mortality

Why Should Physical Therapists Know About Diagnosis?

• PTs must be able to engage in the diagnostic process as part of their overall evaluation → to develop a well-reasoned intervention plan for addressing the patient's problems.

• This process must lead to a decision regarding the probable pathological or pathophysiological cause of the patient's problem.

• Determination of whether physical therapy intervention is the most appropriate to address the underlying pathology of the patient's condition

What is a Diagnosis?

• defined as the process and product of a clinical investigation related to the pathology underlying a patient's or client's symptoms and signs.

• an attempt to identify the target disorder

  • a clinician's application of a diagnostic label represents the best attempt at a shorthand categorization of the patient's or client's condition with a link to the underlying cause of the patient's signs and symptoms

Diagnostic Process

• Physical therapists must make a decision regarding the nature of the pathology and its severity in order to determine whether physical therapy is appropriate to address the patient's condition.

• Deciding on what something is NOT, is being engaged in the diagnostic process

  • Relies on a solid foundation of signs/symptoms of pathology

  • Differential Diagnosis

Importance of Diagnosis

• Even if physical therapy is deemed the appropriate management strategy for the patient’s problem, it remains essential to identify the presence of a medical condition that will affect the outcome of any physical therapy intervention.

• Medical comorbidities must be taken into consideration when designing a physical therapy intervention.

  • For example, the presence of osteoporosis may affect the nature of any intervention provided to a patient with a history of thoracic spine pain, since the patient's symptoms may be related to compression fractures.

Physical Therapists Elaborate on the Diagnostic Label

• even if the pathology is known, the physical therapist must go beyond the diagnostic label and identify how it relates to the patient’s impairments, activity levels, participation, and health.

• In addition, the physical therapist must determine which impairments are causing the activity and participation restrictions, and how they are doing so. Accomplishing this provides the best chance at intervening with respect to the most relevant impairments.

Essentialism

• It is important to determine the anatomical or pathological source of symptoms and to determine the stage of healing, so that appropriate treatment is directed to the appropriate tissue at the appropriate time.

• After the narrowest possible level of cause has been identified, an essentialist approach to treatment is to eliminate or modify the cause

Should Physical Therapists Diagnose Pathology?

• Physical therapists are often vital participants in the process of identifying the pathology that is causing a patient's condition. In many instances, physical therapists further specify the nature of the pathology or its precise anatomical location

• It’s been shown that less than a third of referrals to physical therapy practices were specific as to the nature of the pathology and anatomical location. Many referral diagnoses were not much more than a restatement of the patients' symptoms.

Should Physical Therapists Adopt a Different Definition for Diagnosis Than Other Health Professionals Use?

PT diagnosis implies that when a PT engages in diagnosis, a different type of label results than when a physician engages in diagnosis.

Should Physical Therapists be Expected to Diagnose Given the Current Legal Environment

• Practice Act

• Reimbursement

• PTs has a professional and ethical responsibility, regardless of how the state practice act may read, to use his or her professional judgment to make the most accurate determination of the underlying pathology, to inform the physician of findings that may conflict with the physician's diagnosis, or to suggest tests that might clarify the diagnosis

What Information Should Physical Therapists Use to Make Decisions About Treatment and Prognosis?

• Different approaches are considered more useful for different patients and different practice patterns within the physical therapy profession.

• It is critical for PTs to elaborate on the referral diagnosis with information that further refines the description of patients' disablement, or to further classify the patient within an accepted schema to define the appropriate treatment

International Classification of Functioning, Disability and Health (ICF)

• provide a scientific basis for understanding and studying health and health-related states, outcomes, determinants, and changes in health status and functioning;

• establish a common language for describing health and health-related states in order to improve communication between different users, such as health care workers, researchers, policy-makers and the public, including people with disabilities;

• permit comparison of data across countries, health care disciplines, services and time; and

• provide a systematic coding scheme for health information systems.

Disability

• Universality: anyone can experience a disability; the disabled are not a separate social group

• Parity: between mental and physical health

• Neutrality: positive and negative aspects of functioning

• Environmental Influence

ICF Boxes

• Health condition

• body functions/body structures

• activities

• participation

• environmental factors

• personal factors

Pathology and Cell Injury

• Pathology, in the broadest terms, is the study of disease.

• Disease occurs for many reasons. Some diseases represent spontaneous alterations in the ability of a cell to proliferate and function normally, and in other cases, disease results when external stimuli produce changes in the cell’s environment that make it impossible for the cell to maintain homeostasis.

• But ALL disease/pathology starts are the cellular level

Cell Injury

• Cells have the ability to adapt to an altered environment (internal and/or external)

• Injury begins at the cellular level

• Severity of injury is directly proportional to the severity, extent and duration of the insult

  • Reversible, chronic, irreversible

Reversible Cell Injury

Insult is small or short in duration

Edema results

Stress →

• increased functional demand

• reversible cell injury

Persistent stress → adaptation →

• hypertrophy, hyperplasia

• atrophy, metaplasia, dysplasis, storage

irreversible cell injury

necrosis

Chronic Cell injury

• Sub-lethal stress applied over time can result in cellular adaptations: atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia

  • May have an impact on function, may lower the threshold for injury by other means

• If stimulus is not removed may progress to a more pathological state

Hypertrophy

• Increase in cell size

  • heart and striated muscle do not undergo mitosis

• Physiological vs pathological

  • Biochemical basis

atrophy

decrease in cell size

hyperplasia

• Increase in cell number

  • most other organs

• Physiologic vs Pathologic

• Only cells that can divide will undergo hyperplasia

• Both hyperplasia and hypertrophy result in an increase in organ size

Metaplasia

is the change of cell type from one to another in an effort to deal with a persistent stressor

Smokers

Dysplasia

is an expansion of immature cells and a loss of mature cells

Irreversible Cell Injury - Necrosis

• Aided by cellular enzymes and immune response

• Eventually these products are picked up by the blood stream and can be used clinically as markers of cell death

Mechanism of cell Injury

• Ischemia

• Infectious agents

• Immune reactions

• Genetic factors

• Nutritional factors

• Physical factors

• Chemical factors

• Reactive oxygen species (ROS)

• Cellular Accumulations

Mechanism of Injury: Ischemia

• Hypoxia vs anoxia

• Results in inadequate nutrient delivery and waste removal

• Tissues will attempt to adapt by changing their metabolism with a shift to anaerobic means of ATP production

  • Myocardial metabolism

• Can result from impaired pulmonary gas exchange(organ or cellular) or transport

MOI: Infectious Agents

Bacterial or viral

MOI: Infectious Agents - bacterial

• Invade tissue and releasing toxins

• Bacteria display a preference for tissue type (tissue tropism)

• Much of the damage can result from the immune response

• Flu Pandemic of 1918

MOI: Infectious Agents - viral

• Take over the machinery of the cell in order to self-replicate

• Create adverse processes incompatible with normal function or cause cell lysis through destruction of cell membrane

MOI: Immune Reactions

• normal’ response → allergy → anaphylaxis → auto-immune disease

• Cytokine storm: Flu Pandemic of 1918 and COVID-19

• Autoimmunity

MOI: Genetic Factors

• alterations in the structure or number of chromosomes that induce multiple abnormalities

  • Down’s Syndrome: cardiac malformations, increased susceptibility to severe infections, cognitive and developmental delays, and increased risk of leukemia and Alzheimer's dementia

• single mutations of genes that cause changes in the amount or functions of proteins

  • Cystic Fibrosis

• multiple gene mutations that interact with environmental factors to cause multifactorial disorders.

  • Diabetes: lifestyle and environmental factors induce the expression of the genetic mutations

Down’s Syndrome:

cardiac malformations, increased susceptibility to severe infections, cognitive and developmental delays, and increased risk of leukemia and Alzheimer's dementia

Cystic Fibrosis

single mutations of genes that cause changes in the amount or functions of proteins

Diabetes:

• multiple gene mutations that interact with environmental factors to cause multifactorial disorders.

• lifestyle and environmental factors induce the expression of the genetic mutations

MOI: Nutritional Factors

• Too little : unable to produce proteins at levels consistent with homeostatic needs

• Too much: obesity

MOI: Physical, Mechanical and Chemical Factors

• Physical: trauma, heat, cold, electricity

• Mechanical

  • Load exceeds the failure tolerance of a tissue

  • Loads applied over time can result in decrease ability to heal

MOI: Reactive Oxygen Species

• A free radical is a molecule with an unpaired electron in the outer orbit. Another term for oxygen derived free radicals is reactive oxygen species.

• Free radicals are generated by normal physiologic reduction-oxidation reactions, ultraviolet light, xrays and ionizing radiation, and transitive metals

• Oxidative stress from aging, infection, inflammation, ischemia, radiation, chemicals, drugs

• ROS damages cells by targeting proteins or DNA

MOI: Cellular Accumulations

• Substances can accumulate in cells as a result of damage to the cell, or they can accumulate in the cells as the result of an intrinsic abnormality in metabolic function.

• May or may not cause damage to the cell.

• Substances that commonly accumulate are lipofuscin (product of lipid peroxidation, which accumulates in lysosomes as the cell ages), calcium, protein, iron, fat, cholesterol, glycogen, and pigments.

Review of healing

• Hemostasis (clotting)

• Inflammation (cleaning area)

  • Kill/contain

  • Inflammation

  • Neo-angiogenesis

• Proliferation (building new tissue)

• Remodeling

Immune system - normal actors

• Skin and barriers: Stop germs from getting inside the body.

• Neutrophils: Rush to injury sites first to eat and trap bad germs.

• Macrophages: Large cells that swallow and clear away debris and invaders.

• Dendritic cells: Catch germs and show pieces of them to other cells to sound a larger alarm.

• Natural Killer (NK) cells: Destroy body cells infected with viruses or cancer.

Acute Inflammation

• Vascular Response

  • Clinical manifestations of inflammation are a direct result of this action:

  • Rubor (Redness)

  • Tumor (swelling)

  • Callor (Increase in local temperature)

  • Dolor (Pain)

• Cellular response

  • Healing

Acute inflammation signs

redness, heat, incapacitation, pain, exudate and edema

redness (erythema) and heat

vasodilation, increased blood flow to the injured area

incapacitation

loss of function is related to tissue damage from injury, pain and swelling at the site

pain

increased vascular permeability and accumulation of fluid causes compression in the tissue, inflammatory mediators can also directly elicit a pain response

exudate and edema

extracellular fluid accumulation often in tissues because of increased vascular permeability

Acute vs Chronic Inflammation

• Ongoing injury or repetitive injury to the same tissue

• Chronic inflammation is persistent, > 6 months

• Different cells are involved

  • Monocytes, macrophages and lymphocytes more so than neutrophils

• Tissue is not restored to near-normal

  • Characterized by fibrosis, extensive scarring or granuloma formation

Chronic Inflammation

• pathological

• Inflammation provides a unifying pathophysiological mechanism underlying many chronic diseases

• Manifestations may be similar to acute (i.e. cardinal signs) in addition to systemic signs of illness

The Molecular Basis of Inflammation and Disease

• While diseases such as atherosclerosis, rheumatoid arthritis, cirrhosis, or interstitial lung disease may manifest in very different ways, the same fundamental mechanisms and mediators drive the disease process.”

• What initiates this process appears to be a persistent stimulus that results in chronic inflammation

Commonalities

• The initiation and progression of inflammation involves the activation and secretion of cytokines. Cytokines secreted by cells mediating the pathophysiological events attract leukocytes.

• Chemokines secreted in these diseases mediate a variety of inflammatory reactions. Chemokines and cytokines enhance the expression levels of adhesion molecules which are important in mediating extravasation of inflammatory cells from the general circulation to the focus of the disease process.

• Macrophages play a major role in perpetuating the inflammatory process by maintaining cytokine secretion and preventing the subsidization of the inflammatory process.

Like a Bad Penny …

• Inflammation will come up again and again and again this semester ….

• Important to know the clinical manifestation of inflammation

  • signs, symptoms, diagnostic tests, when it’s getting worse/better