W2 Cellular injury and genetic disease Flashcards
Explain how environmental and genetic factors affect cellular functions.
- Chemical: toxins - posions
- Physical: heat/cold. - hypothermia
hyperthermia - heat exhaustion
- electricity
- trauma
- radiation - Nutritional imbalance: lack of energy (starvation).
- metabolic malfunction deficiency/excess - Ischaemia (lack of blood flow): blood vessel disease, obstruction
- Hypoxia/hypoxaemia (low oxygen): respiratory dysfunction/altitude
- infection
- Immunological response: inflammatory processes
GENETIC ABNORMALITIES: - inherited mutations or other DNA abnormalities → cellular processes → cellilar injurt
- Combo = caused by enviro factors that modify genetic components → (epigenetic alternations; reversible change in cellular state). Somatic mutations (DNA damage, may lead to cancer)
Describe the 4 major mechanisms of cellular injury.
- Direct damage to proteins, membranes, DNA
- ATP depletion Causes: damage to mitochondria, impaired blood flow, low oxygen supply. Less aerobic metabolisim stops. Anaerobic metabolism used. K+ in Na+ out
- Free radicals (oxidative stress and reperfusion injury. This occurs when ATP depletion results from hypoxia/hypoxaemia and eventually the O2 re-enters the cells.
- ↑ intracellular calcium:Cells usually maintain low free intracellular calcium by pumping it out or storing it in calcium stores. Thereby, can damage the cells
Describe the possible outcomes of cellular injury.
Cellular injury can be reversible or irreversible. This would usually depend of the extent of the injury, intensity and duration of exposure.
Hallmarks of reversible injury are:
1. Cell swelling; inability to maintain intracellular ion concerntration
2. fatty accumulation → supply or utilisation,
It becomes irreversible when mitochondria become damaged and calcium homeostasis is impaired.
Explain the main mechanisms of cellular adaptation.
- Cells may respond to these stiumuli or stressors by adapting.
- Adaptation allows the stressed tissue to survive or maintain function
- Adaptation can be physiological (healthy) or pathological (dysfunctional)
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia (reversible) replacement of one cell type with another
- Dysplasia (reversible) deranged cell growth
Distinguish between physiological and pathological cellular adaptation.
Physiological adaptation:
- Hypertrophy with exercise, pregnancy, child growth
- Atrophy with age (cells ↓) brain atrophy normal for age, muscles through lack of use or stimulation.
Pathological adaptation:
Hyperplasia in cancer. Brain atrophy as a result of Alzheimers disease. Cardiac hypertrophy in response to hypertention
Metaplasia (reversible) replacement of one cell type with another, never change completely from original tissue
Dysplasia (reversible) deranged cell growth. Pre-cancerous.
Explain how cellular injury /dysfunction may lead to cellular inclusions.
Stressed cells may fill up with sources of stred energy such as:
→ Lipids; accumlate when supply is ↑ or cellular metabolisim is ↓
→ Glycogen; usually caused by gnetic disorder
→Abnormal protein; genetic or acquired. Often due to proteins with protein folding,
→ Pigments; endogenous or exogenous
→ CALCIUM
Disruption of calcium homeostasis; deposition impairs function of organs such as kidneys, lungs and blood vessels.
DYSTROPIC CALCIFICATION: deposition of crystalline calcium phosphate in injured tissue, Ca+ is released from dead and dying cells, thus this can cause loss of function of the organ or tissue. Mostly common in atherosclerotic lesions and heart valves
Describe the 2 types of cell death and exemplify how they may be triggered.
- NECROSIS
- Unregulated death caused by injury to cells. Causes cells to swell and rupture. Inflammation results. - APOPTOSIS (programmed cell death)
- Tissue renovation : removes cells that are begin replaced or worn out.
- Normal developmental growth processes in body.
- When there are DNA replication errors in cell division
- May be induced by viral infection
Outline and describe the different types of necrosis.
Coagulative: Protein dnaturation in responsee to severe ischamia (rstricted blood supply)
LIQUFACTIVE: Rapid releease of largee amounts of lysomal enzymes (nerves).
CASEOUS: Cells look like cheese, not completeely liquefied, lung.
FAT: from accute inflammation affecting fat tissues. Damaged cells release digestive enymes → break down lipids into free fatty acids.
GANGRENOUS: Nectrotic breakdown of a large amount of tissue, thereby Lack of blood flow to tissues. Wet, dry and gas
Define genetic mutation and explain how it can result in cellular dysfunction.
It is the sequence of the adeninee, cytosine, guanine, thymine bases along a single strand of the DNA molecule which provides the code for a protein product. Gene sequence (DNA) → TRANSCRIPTION (squence of DNA that is copid into mRNA)→ Message (RNA) → Translation (teemplate is read by ribosome, coding an amino acid chain) → Protein product.
PROTEINS: control many biological functions such as
- enzymes
- hormones
- structural components
- transport molecules
contractile fibers (muscles).
Note it can b switched on and off. Many different signals control gene expression (environment)
Genetic mutation are changes in the DNA sequence; may alter an eessential protein or cellular process.
ERRORS in DNA sequence of a gene may lead to
- production of abnormal/non-functional protein
- reduction in th amount of protein produced
-lack of production of a protein.
Types of mutations: Germline cells can result in gneetic disease and be passed on. Mutations in somatic cells an result in non-hereditary cancer
Define and describe the normal composition of a human karyotype.
A karyotype is an individuals seet of chromosomes. 23 pairs (46) 22 autosomal pairs + 1 sex pair. Y= dad X= mum.
Alleles: version of gene from mum and dad
Explain how chromosomal non-disjunction can lead to a chromosomal disorders.
Sometimes chromosomes do no separate correctly during meiosis. The elack of seperation is called chromosomal non-disjunction. → When that gamete joins another to form a new individual, it = incorrect total number of chromosoms (anuploidy).
games w 2 x coppied + gamte w 1 x copy = trisomy (3 chromo)
Games with 0 copy + gamete w 1 x copy = monosomy (1 chromosome)
ABNORMALITIS: other aneusomies usually rsult in miscarriage. Chancs of chromosomal non-disjunction ↑ significantly w age >35
Outline and describe the main categories of genetic disorders.
- AUtosomal dominnant disorders: caused by a mutation on a dominant allele, only 1 mutant copy determines the disease.
- Autosomal recessive disorders: caused by a mutation on a recessive allele. 2 mutant copies are needed to determine thee disease, people with 1 mutant copy are carriers but don’t manifiest the disease.
- Sex linked disorders (X-lined recessive). Mostly recessive. More common in males because they only geet 1 copy of the x-linkd gene
Explain how mitochondrial DNA disorders are inherited and exemplify.
Mitochondria also carry genes mtDNA, inherited by the mother, because sperm nucleus is the only paterenal component remaining in the zygote
Explain how multifactorial disorders may develop and exemplify.
Multifactorial inheritance: combination of genes mutations and environmental factors.
- Congenital abnormalities
- cardiovascular disease
- diabetes mellitus
- metabolic syndrome
Define congenital abnormalities and explain how they may develop
Congenital abnormalities are deletion or damage to chromosoms (tertogens, substances that interfere with foetal development) , changes to the inside of uterus environment, environmental factors. They be develop from genetic, environmental, and %50 unknown
