Patho Exam 1: Cell Function & Growth

ch2 & 4

Elements of Formal Genetics

Locus, Allele, Polymorphism

Homozygous, Heterozygous

Genotype, Phenotype

Dominant, Recessive

Locus

Position of a gene along a chromosome

Allele

A different form of a particular gene at a given locus

Polymorphism

Locus with 2+ alleles that occur with appreciable frequency

Homozygous

Loci on a pair of chromosomes have identical genes

Heterozygous

Loci on a pair of chromosomes have different genes

Genotype

Composition of genes at a given locus; What they have

Phenotype

Outward appearance of the genetics of an organism; What they demonstrate

Dominant

Observable allele (2 found together)

Recessive

Hidden effects (2 allele found together)

Autosomal Dominance Diseases

1. Adult polycystic kidney disease

2. Familial hypercholesterolemia

3. Marfan syndrome

4. von Willebrand disease

5. Huntington’s disease

6. Neurofibromatosis

Adult Polycystic Kidney Disease

Multiple, enlarging cysts develop in both kidneys

APKD Info

• Symptoms: Hypertension, abdominal pain, hematuria (blood in urine), UTIs, kidney stones

• Recurrence: Affected parent has 50% chance of passing it to each child (male/female)

• Age: Cysts can develop early, but symptoms don’t appear till 30-50s

Familial Hypercholesterolemia

Elevated LDL cholesterol

FH Info

• Symptoms: Chest pain, shortness of breath, fatigue, heart attack at a young age, tendon xanthomas & xanthelasma

  • Accelerated development of atherosclerosis (plaque buildup in artery walls) and coronary artery disease

• Recurrence: Affected parent has 50% chance of passing it to each child

  • Homozygous FH occurs when the pathogen is inherited from both parents

• Age: Present from birth, but symptoms can become worse in adolescence/adulthood

Marfan Syndrome

Loose connective tissues caused by FBN1 mutation

Marfan Syndrome Info

• Symptoms: Long limbs, scoliosis, stretch marks

• Recurrence: Affected parent has 50% chance of passing it to each child (male/female)

• Age: Present from birth, but can worsen in adolescence/adulthood

von Willebrand Disease

Common; Deficiency in vWF protein used to form blot clots

vWD Info

• Symptoms: Excessive bleeding and nosebleeds, easy bruising

• Recurrence: Affect parent has 50% of passing it to each child, both male/female

• Age: Present from birth but worsens later into adolescence/adulthood

Huntington’s Disease

Early decay of brain nerve cells

Huntington’s Disease Info

• Symptoms: poor balance and coordination, muscle rigidity, cognitive difficulties

• Recurrence: 50% chance of inheritance, both males/females

• Age: Symptoms don’t appear until 30-50s

Neurofibromatosis

Tumors grow on the nerve tissues of the body

Neurofibromatosis Info

• Symptoms: Tumors all over body, learning difficulties, headaches

• Recurrence: 50% chance of inheritance, both males/females

• Age: Different features appear at different ages. Tumors grow later in life

Autosomal Recessive Info

• Both parents are heterozygous carriers, male/female equally effected

• Recurrence risk for offspring is 25%

• Dramatically increases the recurrence risk of recessive disorders

Consanguinity

Mating of 2 related individuals

X-Linked Inheritance

Genetic conditions caused by mutations; mostly X

Hemophilia A

Bleeding disorder due to impaired blood clotting

Hemophilia A Info

• Symptoms: Easy bruising and nosebleeds, prolonged bleeding after injuries, hemarthrosis

• Recurrence: Typically affects males, only females are carriers

Duchenne Muscular Dystrophy

Dystrophin deficiency caused by DMD gene mutations

Duchenne Muscular Dystrophy Info

• Symptoms: Difficulty running/jumping/walking, loss of mobility, respiratory weakness, cognitive difficulties

• Recurrence: Typically affects males, and begins in early childhood.

Albinism

Reduced/Absent melanin production

Albinism Info

• Symptoms: Reduced pigmentation in skin/hair/eyes, light sensitivity

• Recurrence: If both parents are carriers, 25% chance of having an (un)affected child and 50% of the child being a carrier

Cell Adaptations

1. Size

2. Number

3. Form

Cell Size

1. Atrophy

2. Hypertrophy

Atrophy

Decrease in cell size/muscle

Hypertrophy

Increase in cell size

Physiologic Hypertrophy

Increased demand, hormone stimulation, growth factors

Pathologic Hypertrophy

Chronic hemodynamic overload

Hyperplasia

Increase number of cells and rate of mitosis

Metaplasia

Replacement of adult cells

Dysplasia

Deranged cell growth of a specific tissue

Cell Injury

Cell unable to maintain homeostasis after insult/stress

Hypoxic Injury

Common cause of cell injury; insufficient oxygen supply to body cells

Hypoxic Injury Causes

Ischemia, Anoxia, loss of hemoglobin, decreased RBC production

Ischemia

Reduced supply of blood

Anoxia

Total lack of oxygen caused by obstruction

Ischemia-Reperfusion Injury

Restoration of blood flow and O2 after ischemia

Free Radicals

Highly reactive molecule with unpaired electron

Chemical/Toxic Injury Causes

1. Xenobiotics

2. Chemical Agents

3. Alcohol

4. Street Drugs

Unintentional/Intentional Injuries Causes

1. Blunt Force

2. Sharp Force

3. Gunshot Wounds

4. Asphyxiation

5. Medical Errors

Pigment Types

1. Endogenous

2. Blood Proteins

Endogenous Pigments

Melanin: UV light, albinism

Blood Protein Pigments

hemochromatosis, hemosiderosis, bilirubin/jaundice

Pathologic Calcification

1. Dystrophic

2. Metastatic

Dystrophic Calcification

Deposit of calcium salts in injured tissue

Dystrophic Calcification Info

• Occurs in dead/dying tissue

• Gritty, sand-like grains → firm, hard rock material

• Location: atheromatous lesions, injured aorta and large blood vessels, damaged heart valves

Metastatic Calcification

Increased serum calcium levels (hypercalcemia)

Metastatic Calcification Info

• Occurs in normal tissues

• Caused by diseases, cancer, intoxication, immobilization

• Location: lungs, renal tubules, blood vessels

Urate

Hyperuricemia → Gout

Cell Death Types

1. Necrosis

2. Apoptosis

3. Autophagy

Necrosis

Rapid loss of plasma membrane structure, organelle swelling, mitochondrial dysfunction

Necrosis Types

1. Coagulative

2. Liquefactive

3. Caseous

4. Fatty

5. Gangrenous

Coagulative Necrosis

Acidosis develops and denatures the enzymatic and structural proteins of the cell

Liquefactive Necrosis

Cells die, but catalytic enzymes are not destroyed

Caseous Necrosis

Form of coagulative necrosis – dead cells persist indefinitely

Fatty Necrosis

Cells dissolve by lipase

Gangrenous Necrosis Types

1. Dry

2. Wet

3. Gas

Dry G Necrosis

Affected tissue slowly becomes dry and shrinks – skin wrinkles and changes to dark brown/black

Wet G Necrosis

Affected area is cold, swollen, and pulseless – skin is moist, black, and under tension

Gas G Necrosis

Type of wet gangrene caused by tissue infection

Apoptosis

Fallen apart cells (suicide)

Autophagy

Process of cell eating itself

Somatic Death

Death of the entire body

Somatic Death Phases

1. Pallor mortis

2. Algor mortis

3. Rigor mortis

4. Livor mortis

5. Putrefaction

6. Decomposition

7. Skeletonization

Pallor mortis

1st stage of death – 15min - 2hrs after

Algor mortis

Body temperature begins to change

Rigor mortis

Begins within 6hrs after death; muscles become rigid, lasts up to 12-24hrs

Livor mortis

Discoloration 8-12hrs after death

Putrefaction

Body loses cohesiveness and gas begins to build up