PHM143

Tips for the midterm

There are 5 questions for each hour of lecture. This means that no matter how hard a concept is, there will probably only be a single question about it (the exception being Hoffman's section, where he uses case studies which incorporate all concepts).

Hoffman's section was the hardest by far, so be sure to study it closely (he also has the most questions on the midterm). The flashcards mostly go over concepts, but he expects you to know random facts as well. The majority of the questions were case studies, so if you only understand the concepts you'll still get 80% of his questions right.

Crandall's section is ezpz, don't spend too much time on it. The rest of the midterm is fair.

NOTE: Important flashcards (in my opinion) are marked by asterisks (**).

Yes they are.

What are some terms which describe change in cellular growth and differentiation?

Hypertrophy: increase in size of cells/organ.

Hyperplasia: increase in number of cells.

Atrophy: reduction in size of cells/organ.

Metaplasia: reversible change in which one differentiated cell type is replaced by another.

What are some constitutional factors which contribute to disease?

Hereditary: genetic abnormalities.

Non-hereditary: age, gender, etc.

What are some environment factors which contribute to disease?

Dietary deficiencies.

Living external agents: bacteria, viruses.

Non-living external agents: burns, etc.

Define a cell.

Structural, functional, and biological unit of all organisms. Self-replicating. Semi-permeable membrane which contains biomolecules (protein, nucleic acids, etc.).

What are some causes of cell injury?**

Oxygen deprivation.

Physical agents.

Chemical agents and drugs.

Infectious agents.

Immunologic reactions.

Genetic alterations.

Nutritional imbalances.

What are some mechanisms of cell injury?**

Depletion of ATP.

Influx of intracellular Ca2+/loss of Ca2+ homeostasis.

Mitochondrial damage.

Accumulation of ROS.

Defects in membrane permeability.

What are some of the downstream effects of ATP depletion?**

K+ efflux, leading to ER and cellular swelling.

Lowered pH, leading to clumping of nuclear chromatin.

Lower protein synthesis, leading to lipid deposition.

What are some downstream effects of intracellular Ca2+ influx?**

Damaged ATPases, leading to lower ATP production.

Activation of phospholipases, reducing membrane stability.

Activation of proteases, reducing membrane stability.

Activation of endonucleases, leading to chromatin damage.

Describe necrosis and apoptosis.

Necrosis is the PREMATURE death of cells, often caused by infection or interruption of blood supply. Enzymatic digestion of cells and denaturation of proteins follow necrosis.

Apoptosis is the NATURAL death of cells. It is a tightly regulated process which serves to protect an organism's integrity.

Describe coagulative necrosis.**

Occurs when: dead tissue is preserved for a span of time (heart attack).

Characterized by: intracellular acidosis and inhibition of proteolysis (enzymes are denatured by lower pH).

What is an infarct?

Localized area of coagulative necrosis.

Describe liquefactive necrosis.**

Occurs when: Focal bacterial or fungal infections.

Characterized by: Accumulation of inflammatory cells, digestion of dead cells, presence of pus, hypoxic death of cells within CNS.

Liquefactive \= cells look liquefied.

Describe caseous necrosis.**

Occurs when: Bacterial or fungal infections.

Characterized by: white and cheesy appearance of cells, granulomatous inflammation (type of inflammation where macrophages accumulate because infection is not eliminated

).

Caseous \= casein (cheesy look).

What biochemical changes occur in apoptotic cells?**

Protein cleavage.

DNA breakdown.

Protein cross-linking.

Phagocytic recognition.

What are some morphological and biochemical differences between apoptosis and necrosis?**

Apoptosis: cytoplasm shrinks, PM blebs w/o loss of integrity, aggregation of chromatin at nuclear membrane, formation of apoptotic bodies, ATP-dependent.

Necrosis: cytoplasm swells, loss of membrane integrity, disintegration of organelles, no vesicle formation just lysis, not energy-dependent.

What are some sources of genetic disorders?**

Single gene alteration.

Interaction of many genes.

Patterns of gene expression (epigenetics).

What are the 3 forms of inherited colour blindness?

Monochromacy: cannot distinguish colours, cones are missing.

Dichromacy: one of the colours cannot be seen, one type of cone is missing.

Anomalous trichromacy: one of the cones has altered spectral sensitivity (sees different wavelength).

Which chromosome contains the most common mutation for colour blindness?**

The X chromosome. Which is why 8% of males and only 0.5% of females have altered colour vision.

What are some tests which can be used to screen for Down syndrome during pregnancy?

Amniocentesis (99% detection rate, very low false positives, can damage/abort the fetus).

AFP, estrol, hCG, INHA (81% detection rate, 5% false positives, non-invasive and done at 15-20 weeks).

Ultrasound (85% detection rate, 5% false positives, non-invasive and done at 10-13 weeks).

Can combine the last two tests to get a 95% detection rate and 5% false positive.

What is a thalassemia?**

Genetic disorder which alters structure of one or both subunits of Hb. Symptoms range from mild to severe anemia. Can be treated with blood transfusions and a generally healthy lifestyle.

What is a sickle cell CRISIS and what different types of crises are there?**

Crisis: circulation issues and lowered oxygen due to sickle cell anemia.

Vaso-occlusive crisis: sickle cells blocking blood flow (leads to necrosis, pain, ischemia). Treated with morphine.

Spenic sequestration crisis: sickle cells accumulate in spleen and spleen function is compromised (leads to splenectomy or death). Treat by removing spleen.

Aplastic crisis: parvovirus B19 shuts down RBC production, patients unable to replace crappy sickle cells (leads to death). Treat with blood transfusion.

Haemolytic crisis: rapid loss of RBCs, especially in G6PD deficient individuals because they are slower at removing ROS. Treat with blood transfusion.

Which enzyme is defective in phenylketonuria (PKU)? What are symptoms of PKU?**

Phenylalanine hydroxylase (PAH), which converts phenylalanine (hydrophobic) into tyrosine (hydrophilic). Phenylalanine will accumulate in the body, especially the brain.

Leads to abnormal brain development, seizures, mental retardation.

Can be mitigated by having a diet low in phenylalanine. One can screen for PKU early on with blood sample.

What are the two forms of PKU?**

PAH enzyme deficiency (98%): Restrict phenylalanine intake, especially in childhood.

Biopterin-deficient PKU (2%): biopterin is a cofactor for PAH. Can be treated with life-long supplementation of biopterin and no dietary restrictions are necessary.

Which protein is mutated in cystic fibrosis**

Cystic fibrosis transmembrane conductance receptor (CFTR), which is responsible for chloride ion tranfer. Mucous is thick and sticky, which leads to increased chance of infections (especially lungs).

Heterozygotes of the mutation may be protected from cholera because decreased chloride secretion into the GI tract leads to decreased water secretion. Less water secretion means less severe diarrhea, which is typical of cholera bacteria infection.

How do you treat CF?**

Use medications to control infections and inflammation. Antibiotic resistance will eventually develop, which causes the death of the CF patient.

Change diet to include lots of fat, protein, calories, and fat soluble vitamins (A/D/E/K) to compensate for poor absorption.

Lung transplant. But other problems will remain.

What is the cause of muscular dystrophy?**

Multiple genetic mutations. Causes progressive weakness and degradation of voluntary muscles.

Duchenne MD is X-linked and causes a mutation in the dystrophin gene.

Which two problems can arise from neural tube disorders?**

Spina bifida: incomplete closing of backbone and membranes around the spinal cord. Leads to neonatal death or life-long paralysis.

Anencephaly: absence of large part of the brain. Miscarriage, still born, or brief live birth.

Can screen for these conditions by looking for alpha fetoprotein during pregnancy.

Preventable by folic acid supplementation during pregnancy.

How does the half-life of albumin and prothrombin differ? What is the clinical significance of this?**

Both albumin and prothrombin are made in the liver, so lowered levels of these proteins signal damage to the liver.

Albumin has a half-life of 3 weeks in the blood, thus only large, sustained damage to the liver will result in change of albumin levels.

Prothrombin has a half-life of a few hours in the blood, so less damage to the liver is required to reflect a change in prothrombin levels. Less prothrombin is reflected in longer clotting time.

What is cholestasis?

Stoppage of bile flow.

Which protein is a general marker for all liver diseases?**

Gamma-glutamyltransferase. If it is found in blood, your liver probably isn't very happy.

What are some routine liver biochemistry tests?**

Bilirubin: tests for hepatocyte health, biliary tract patency.

Alkaline phosphatase (ALP): biliary tract patency.

Transaminases (AST and ALT): damaged hepatocytes.

Which specialty molecules can be measured in the bloodstream to screen for different liver conditions? Match the corresponding liver condition with each molecule.

Ammonia: ammonia levels rise with metabolic (hepatocyte) insufficiency because urea is made in the liver.

Alpha-fetoprotein: alpha-fetoprotein levels rise with hepatoma (tumour of the liver).

5'-nucleotidase: increased in cholestasis

LDH: metastases

Alpha1-antitrypsin, caeruloplasmin, ferritin: cirrhosis etiology

Immunoglobulins and autoantibodies: chronic disease.