Exam 1 - final Q

It is important that due to diversity, what two factors are not necessarily identical in any two individuals

Heath structure and function

What are the four interrelated topics that correspond to pathophysiology?

1) Etiology

2) pathogenesis

3) clinical manifestations 

4) Treatment implications 

Etiology

causes or reasons of disease

Pathogenesis

development of disease

Clinical manifestations

signs, symptoms, stages, course

treatment implications

general treatment strategies

True or false: Are most diseases multifactorial

True 

A patient presents with hair loss due to undergoing chemotherapy, is this an example of an iatrogenic cause

yes

Idiopathic

cause is unknown

Iatrogenic

cause results from unintended or unwanted medical treatment

Coronary heart disease is a multifactorial disease, what are some reasons as to what classifies a multifactorial disease 

Several different etiologic factors (risk factors) that can contribute to disease development 

• Genetic disposition

• Smoking

• Diet

• high BP

• stress

what an pathogenesis be defined as

the evolution or development of disease, from initial stimulus to ultimate expression of manifestations of the disease 

Signs are defined as what

objective or observed manifestation of disease

• clinical examination

• Lab tests, diagnostic imaging

• vomiting

• enlarged lymph nodes

• elevated fasting blood sugar

Symptoms can be defined as

Subjective feeling of abnormality in the body

• headache

• nausea

Which of the following is an example of the clinical manifestation known as a symotom

Headache

What is the difference between a latent period vs a prodromal period

Latent → time between exposure of tissue to injurious agent and first appearance of signs and/or symptoms 

Prodromal period → Time during which first signs and/or symptoms appear indicating onset of disease (often nonspecific) 

Which is the phase that refers to a period during an illness when the signs/symptoms temporarily become mild. silent, or disappear 

Latent period 

Sensitivity

probability that a test will be positive when applied to a person with a particular condition

• false negatives → % of people with the condition will test negative 

Specificity

The probability that a test will be negative when applied to a person without a particular condition 

• false positives → % of persons without condition will test positive 

Strep throat swab with a sensitivity of 80% means that 20% of people with the condition will test negative making this a ____

False negative 

Patterns of disease

• Endemic

• Epidemic

• Pandemic 

Endemic

Native to a local region

Epidemic

spread to many at the same time

Pandemic

spread to a large geographic area

Levels of prevention 

• Primary

• secondary

• tertiary 

Primary

altering susceptibility or reducing exposure for susceptible persons

• vaccine 

secondary

early detection, screening, and management of disease

• Screening (mammogram) 

Tertiary

rehabilitation, supportive care, reducing diasability, nd restoring effective functioning 

• physical therapy 

Which of the following is an example of secondary prevention

Preforming monthly breast examinations and screening for cancer

A patient with high BP who is otherwise healthy is counseled to restrict sodium intake. What is this an example of

Secondary prevention 

A 17 year old college bound student receives a vaccine against an organism that causes meningitis. This is an example of 

Primary prevention 

What are the three ways that cells respond to environmental changes and injury

1) withstand

2) adapt

3) cell death 

Withstand

the assault and return to pre-injury normal state

• return

• Injury is mild and short-lived 

Adapt

to a persistent but sublethal change/injury by changing structure or function

• reversible 

Cell death

By necrosis or apoptosis

• irreversible 

Another word for oncosis is

Hydropic swelling

what is the definition of oncosis (hydropic swelling)

Cellular swelling because of accumulation of water

• first manifestation of most forms of reversible cell injury

• results from malfunction of sodium-potassium pump with accumulation of sodium ions within the cell → water enters the cell 

• Severe swelling can cause organ enlargement (megaly)

  • dilation (swelling) of endoplasmic reticulum and mitochondria 

Intracellular accumulation is characterized by what

• Accumulation of excessive amounts of normal intracellular substances

  • Lipids 

  • Carbohydrates

  • Proteins

  • Inorganic pigments 

• Accumulation of abnormal substances from faulty metabolism or synthesis 

  • denatured and abnormally folded intracellular proteins

  • Inorganic particles

• Accumulation of pigments or particles that cell is unable to degrade or digest

  • tar, mineral dusts, coal, silica, iron, lead, silver

What is an example of physiologic hypertrophy

Increase in skeletal muscle size in response to exercise

What is an example of pathologic hypertrophy

heart muscle enlargement in response to high BP

what is hypertrophy 

Increase in cell mass accompanied by an augmented functional capacity in response to physiologic and pathophysiologic demands

• increased cell size

What are the two categories of irreversible cell injury

Necrosis and Apoptosis

What is necrosis

usually due to ischemia or toxic injury

• cell rupture 

• spilling of contents into the extracellular fluid 

• inflammation 

What is apoptosis

occurs from injury that does not directly kill the cell but triggers “suicide”

• no rupture 

• no inflammation 

What are the four types of necrosis

1. coagulative → most common

2. Liquefactive 

3. Necrosis

4. Caseous necrosis

Coagulative necrosis

most common (not enough oxygen supply) 

• begins with ischemia

• loss of plasma membranes ability to maintain electrochemical gradient

• influx of calcium and mitochondrial dysfunction

• degradation of plasma membrane and nuclear structures

• affected area is composed of degenerated proteins and is relatively solid 

Liquefactive necrosis

• occurs with rapid dissolution of dead cells

• liquification by lysosomal enzymes 

• formation of abscess or cyst form dissolved dead tissue 

Fat necrosis

• Death of adipose (fatty) tissue

• Starts with release of degradative enzymes 

• Fats are hydrolyzed into glycerol and fatty acids

• usually result of trauma or pancreatitis

• Appears as a chalky white area of tissue 

Caseous necrosis

• characteristic of lung damage due to tuberculosis

• resembles clumpy cheese 

What is the most common form of necrosis

Coagulative

What is gangrene defined as

cellular death in large area of tissue resulting from interruption of blood supply to a particular part of the body

What are the three types of gangrene

1. Dry gangrene

2. Wet gangrene

3. gas gangrene 

Dry gangrene

Form of coagulative necrosis is characterized by blackened, dry, wrinkled tissue separated by a line of demarcation from healthy tissue

Wet gangrene

• form of liquefactive necrosis

• typically found in internal organs

• can be fatal

Gas gangrene

• results from infection of necrotic tissue by anaerobic bacteria (clostridium) 

• Characterized by formation of gas bubbles in damaged muscle tissue 

• Can be fatal → cause sepsis 

Does apoptosis cause an inflammatory response

no

What is ischemia and hypoxic injury

causes of cellular injury

• Tissue hypoxia is most often caused by ischemia

• ischemia is he most common cause of cell injury

• Ischemia is defined as the lack of blood supply

• Hypoxia is defined as the lack of oxygen

Can restoration of oxygen worsen cell injury rather than reversing it

yes it can exacerbate cell injury

Nutritional deficiencies may result from 

• poor intake 

• altered absorption

• impaired distribution by circulatory system

• Inefficient cellular uptake

What are the five causes of cellular injury

1. Ischemia/hypoxic injury 

2. Nutritional injury

3. Infectious/immunologic injury

4. Chemical injury 

5. Physical/mechanical injury 

Ischemia/hypoxia-reperfusion injury

• calcium overload which can lead to apoptosis

  • occurs because ATP stores are depleted and cell is unable to control ion flux across the membrane

• Formation of free radicals (oxygen radicals)

• Subsequent inflammation

Nutritional injury

• Adequate amount of fats, carbohydrates, proteins, vitamins, and minerals are essential for normal cellular function

• Most essential nutrients must be obtained form external sources

• Certain cell types = more prone to injury

  • iron deficiency primarily affects RBC

  • Vitamin D deficiency affects bones 

Nutritional excess can also cause cellular injury

• BMI > 25 kg/m² → health risk

• BMI > 30 kg/kg/m² → obesity 

Infectious and immunologic injury

• bacteria can injure cells in a variety of ways

  • depends on access to the cell and success in altering cellular functions

  • Release of exotoxins

  • Release of endotoxins

  • Added injury

• Viruses gain entry to cells, replicate inside

  • some viruses can make the immune system kill the cell → hepatitis B

Chemical injury

Toxic chemicals, poisons or pollutants can cause cellular injury both directly and indirectly by becoming metabolized into reactive chemicals by the body

Example of direct cell injury

lead poisoning → effect on neural tissue

Example of indirect cell injury

carbon tetrachloride (formerly used as a cleaning agent) is converted to the free radical CCL3- by liver cells which can cause cell injury and liver failure

Physical and mechanical injury

• extremes in temperature

• abrupt changes in atmospheric pressure

• mechanical deformation

• electricity

• ionizing radiation → has two primary effects

  • 1) Genetic damage

  • 2) acute cell destruction

    • hematopoietic, gonadal, mucosal, fetal 

what is death of the entire organism called

Somatic death

What is the cellular basis of aging

Is the cumulative result of two factors that cause cellular and molecular damage

1. progressive decline in proliferation and reparative capacity of cells

2. Exposure to environmental factors 

What is the programmed senescence theory

Aging is the result of an intrinsic genetic program

• after a certain number of division cycles a critical point is reached at which time cells become dormant or die 

Free radical theory

aging results from cumulative and progressive damage to cell structure

What are the four groups of genetic disorders

1. Chromosomal abnormalities

2. Mendelian single-gene disorders

3. Non-mendelian single-gene disorders 

4. Polygenic and multifactorial disorders  

Chromosomal Abnormalities

Result from:

• Abnormal number of chromosomes 

  • Aneuploidy

    • Monosomy

      • Turner syndrome → monosomy X no Y chromosome

    • Polysomy

      • Down syndrome → Trisomy 21 

      • Edwards syndrome → Trisomy 18

      • Patau syndrome → Trisomy 13

      • Klinefelter syndrome → XXY but can have more X’s

• Alterations to the structure of one or more chromosomes 

  • Usually a result of errors in separation during meiosis 

    • Translocations

    • Inversions

    • Deletions

      • Cri du Chat syndrome → part of p arm on Chromosome 5 

    • Duplications

Aneuploidy

abnormal number of chromosomes either > 46 or < 46 in humans

• Usually caused by nondisjunction

• resulting gametes have 22 and 24 chromosome pairs or 45 or 47 individual chromosomes 

What is an example of autosomal aneuploidy

• Down syndrome or Trisomy 21 (extra copy of chromosome 21)

• Edwards syndrome or Trisomy 18 (extra copy of chromosome 18)

• Patau syndrome or Trisomy 13 (extra copy of chromosome 13)

Trisomy 21

Down syndrome

• associated with advanced maternal age

• 1 in 700 live births 

• Extra chromosome on 21 

Trisomy 18

Edwards Syndrome

• Most affected pregnancies are lost before term

• Babies are born small and have heart defects

• CNS deformities

• Severe intellectual disability 

• Extra chromosome 18 

trisomy 13

Patau syndrome

• Most affected pregnancies are lost before term

• Abnormal brain structure

• Severe intellectual disability

• Associated with high maternal age

• Extra chromosome 13

Sex chromosome aneuploidies

Aneuploidies involving the sex chromosomes X or Y are much better tolerated than autosomal aneuploidies

Example of sex chromosome aneuploidy

• Klinefelter Syndrome → extra X

• Turner Syndrome → missing a Y 

Klinefelter Syndrome

• Most common sex chromosome abnormality 

• Affects males 

• Usually 1 extra X chromosome → XXY

  • can be more than one 

• 1 in 600 live-born males

• Abnormal sexual development and feminization

• Lack of secondary sex characteristics during puberty 

• Marginally impaired intelligence

• Testosterone therapy reduces feminine characteristics

Turner syndrome

• Affects females

• 1 in 2500 live female births

• Monosomy X → normal X and no Y chromosome 

• Female phenotype with no developed ovaries

• Second X chromosome missing or structurally abnormal usually from father’s chromosome 

• Most fetuses lost during pregnancy

• Short stature

• webbing of neck

• Congenital heart defects

Cri du Chat syndrome

• example of a chromosome structural abnormality

• Deletion of part of the short arm of chromosome 5

• 1 in 50,000 births

• Characterized by round face, severe mental disability and heart anomalies

• Cry of infant sound like cat cry

  • due to laryngeal malformation

Mendelian single-gene disorders 

Result from alterations or mutations of single genes

• autosomal or sex chromosome

• dominant or recessive 

Autosomal-Dominant disorders

Caused by mutation of a specific autosomal gene

• Marfan Syndrome

• Huntington Disease

Marfan disorder is what type of tissue disorder

Marfan syndrome

Marfan Syndrome

• Autosomal dominant

• connective tissue disorder

• tall, slender, long, thin fingers and legs

• Cardiovascular lesions most life threatening

• Aorta tends to be weak → dilation and rupture

• Traced to mutations is fibrillin 1 gene on chromosome 15 

Marfan syndrome is traced to which mutation and low levels cause

Mutation in fibrillin 1 gene on chromosome 15 and low levels of fibrillin leads to weakening of the connective tissue

Huntington disease

• autosomal dominant

• Primarily affects neurologic function 

• Symptoms appear after age 40

• Mental deterioration involuntary arm/leg movements

• Parent may transmit to offspring before becoming aware of a defective gene 

• Prevalence 1 in 20,000

• Gene abnormality on chromosome 4 

• Abnormal huntingtin protein is produced which causes nerve degeneration

An abnormal amount of what protein is produced in Huntington disease that causes nerve degeneration 

Huntingtin protein 

Autosomal recessive disorders

• mutation of autosomal recessive gene

• Albinism → lack of pigmentation from disrupted melanin synthesis

• Phenylketonuria (PKU) → inborn error of metabolism cannot metabolize phenylalanine 

• Cystic fibrosis → defect in membrane transporter for chloride ions in epithelial cells called CFTR

Do males always express the disease for a sex-linked X disorder

yes

Sex-linked X disorders

• mutation of sex chromosome (almost always X)

• Female express disease when both X chromosomes have mutation (rare)

• Males always express disease

• almost always male but females are carriers

• father transit to daughters and none to sons 

• Hemophilia A → bleeding disorder from lack of factor VIII

Non-mendelian single-gene disorders

• long triplet mutations such as fragile X syndrome

  • Long repeats of 3 nucleotides (CGG) in the FMR1 gene on the X chromosome

  • causes mental retardation 

• Mitochondrial DNA mutations 

  • Tend to cause dysfunction in tissues with high utilization of ATP

  • father does not pass along mitochondria only mother 

• Genetic imprinting 

  • only one parental copy of a gene is naturally silenced by methylation 

  • Prader-will syndrome → uncontrolled eating and obesity and metal retardation

  • Angelman syndrome → metal retardation and uncontrolled smiles

Polygenic and multifactorial disorders 

Multifactorial traits do not follow clear cut modes but tend to “run in families” 

• common compared to single gene and chromosomal abnormalities

  • high BP

  • cancer

  • diabetes

  • atherosclerosis

• Environmentally induced congenital disorders

Environmentally induced congenital disorders

• errors in fetal development

• Teratogens → factors/agents that cause congenital malformations

  • chemicals

  • radiation

  • viral infections 

• Susceptibility depends on

  • amount of exposure

  • developmental stage of the fetus when exposed

  • prior condition of the mother

  • genetic predisposition of fetus

Periods of Fetal vulnerability

• before 3rd gestation week 

• 3rd to 9th week

• after 3rd month 

Between which weeks is the embryo most susceptible to teratogenesis

3rd to 9th week especially during the 4th and 5th weeks during organ development

when does teratogen exposure either damages very few cells or so many that embryo cannot survive 

before 3rd gestational week