CP Path Outlines

Question 1

What is the standard of care treatment for immune / acquired thrombotic thrombocytopenic purpura (TTP)?

Answer 1

Therapeutic plasma exchange and immunosuppression

Treatment of TTP requires emergent initiation of therapeutic plasma exchange (TPE) and immunosuppressive medications (such as rituximab).

Question 2

Why is high volume plasma transfusion not recommended for TTP?

Answer 2

It may lead to fluid overload

The high volume of plasma needed for TTP remission can cause fluid overload.

Question 3

In TTP, why is platelet transfusion contraindicated?

Answer 3

It is contraindicated except in severe bleeding

Platelet transfusion can worsen the condition in TTP.

Question 4

What are the characteristic microscopic peripheral blood findings in an acute episode of immune / acquired thrombotic thrombocytopenic purpura (TTP)?

Answer 4

• Anemia
• Schistocytosis
• Thrombocytopenia

TTP is a type of thrombotic microangiopathy characterized by microangiopathic hemolytic anemia and thrombocytopenia.

Question 5

What does schistocytosis indicate in the context of TTP?

Answer 5

Microangiopathic hemolytic anemia

Schistocytosis is a peripheral blood finding substantiating anemia from intravascular hemolysis.

Question 6

What type of mutations are involved in hereditary persistence of fetal hemoglobin (HPFH)?

Answer 6

• Large deletions of the β globin locus
• Point mutations in γ globin promoters

These mutations increase γ globin expression and HbF production.

Question 7

A 48 year old man undergoing routine screening is found to have HbF 35%, HbA1 63.5% and HbA2 1.5% on hemoglobin electrophoresis. His red cell indices are normal and he has no evidence of anemia. What is the most likely underlying genetic mechanism?

Answer 7

hereditary persistence of fetal hemoglobin (HPFH): Large deletions involving the β globin locus or point mutations in γ gene promoters

Question 8

What is the structure of HbF (Fetal)?

Answer 8

𝛼2 𝛾2 (Alpha/Gamma)

HbF is primarily found in fetuses and newborns.

Question 9

What is the structure of HbA1 (Adult)?

Answer 9

𝛼2 𝛽2 (Alpha/Beta)

HbA1 is the main type of hemoglobin in adults.

Question 10

What is the structure of HbA2 (Minor Adult)?

Answer 10

𝛼2 𝛿2 (Alpha/Delta)

HbA2 is present in small amounts in adult blood.

Question 11

What is the normal adult level of HbF?

Answer 11

< 1%

HbF levels are typically very low in adults.

Question 12

What is the normal adult level of HbA1?

Answer 12

95% - 98%

HbA1 constitutes the majority of hemoglobin in adults.

Question 13

What is the normal adult level of HbA2?

Answer 13

2% - 3%

HbA2 is present in small quantities in adult blood.

Question 14

What does high levels of HbF in adults indicate?

Answer 14

Hereditary persistence (HPFH) or thalassemia

Elevated HbF levels in adults can suggest specific genetic conditions.

Question 15

What condition is indicated by elevated HbA2?

Answer 15

β-thalassemia trait

Increased HbA2 levels can be a marker for this genetic condition.

Question 16

When do you start treatment with statins?

Answer 16

10 year CVD risk is ≥ 10%

Question 17

Which of the following drugs is eliminated from the body following a nonlinear (exponential) kinetic elimination process?
* Aspirin
* Ethanol
* Heparin
* Phenytoin
* Propranolol
* Warfarin

Answer 17

Propranolol (and > 95% of available drugs) follow first order elimination kinetics (i.e. constant fraction per unit time). The remaining < 5% of drugs follow zero order elimination kinetics (i.e. constant amount per unit time).

Question 18

Define Zero-Order Kinetics

Answer 18

Zero-Order (Constant Amount Each Time)
✅ What happens:
You lose the same amount every time
It does NOT depend on how much you have left
🍬 Example:
Start with 100 candies, eat 10 every hour:
1 hr → 90
2 hr → 80
3 hr → 70
👉 Always losing 10 each hour
(👉 Half-life is NOT constant)

Question 19

Define First Order Kinetics

Answer 19

First-Order (Percentage Each Time)
Exponential
✅ What happens:
You lose a percentage of what’s left
It depends on how much you have
🍬 Example:
Start with 100 candies, eat 50% every hour:
1 hr → 50
2 hr → 25
3 hr → 12.5
👉 Big drop at first, then slower
(Half-life is CONSTANT)

Question 20

Prevalence and Significance of First vs Zero Order Kinetics for Drugs

Answer 20

🔹 First-Order (Most Drugs)
Most drugs leave your body in a first-order way.
✅ What that means:
Your body removes a percentage of the drug each time
Example:
100 mg → 50 mg → 25 mg → 12.5 mg
💡 Why this happens:
Your liver and kidneys work proportionally
More drug → faster removal
Less drug → slower removal
⭐ Key point:
Constant half-life (very useful for doctors!)
🔹 Zero-Order (Less Common, Special Cases)
Only a few drugs follow zero-order kinetics.
✅ What that means:
Body removes a fixed amount, no matter how much is there
⚠️ Why this happens:
The body’s enzymes get overloaded (saturated)
They can’t go any faster
🔹 Common Zero-Order Examples (Important!)
You should remember these:
Ethanol (alcohol)
Phenytoin (seizure medicine)
Aspirin (at high doses)
👉 These are often taught as:
“Zero-order = rare but dangerous”
🔹 Why First-Order Is Safer
Predictable
Easy dosing
Less risk of sudden buildup
🔹 Why Zero-Order Can Be Risky
Drug can build up quickly
Small extra dose → big increase in level
Higher risk of toxicity

Question 21

The level of which lab is inversely related to the risk of cardiovascular disease?

Answer 21

High density lipoprotein (HDL)

Question 22

HDL cholesterol is called the good cholesterol because it

Answer 22

Transports cholesterol from tissues to liver for excretion

Question 23

Which type of urinary cast has serrated edges and is an indicator of end stage renal disease?

Answer 23

Waxy cast is seen in the setting of prolonged low urine flow.

Question 24

Which machine learning method was inspired by the way our visual cortex processes images through receptive fields, whereby retinal neurons receive stimuli from different regions of the visual field and information from multiple retinal neurons are relayed to neurons further down the chain?

Answer 24

Convolutional neural network (CNN) CNN has a feed forward neural network architecture composed of convolution and pooling (downsampling) layers, followed by 1 or more fully connected layers. Convolution or pooling operations are carried out on information from 1 layer and the results are passed on to a deeper layer of the network. CNN has been used on digital slides to aid in identifying histological structures, such as mitosis, nuclei and regions with cancer metastasis.

A convolutional neural network (CNN) is a type of computer model that looks at images and learns to recognize patterns in them.
It works step by step, passing information forward through different layers.
First, it uses convolution layers to scan the image and find important features (like edges, shapes, or textures).
Then, pooling layers shrink the image a bit, keeping only the most important information.
At the end, fully connected layers use all that information to make a final decision (like “this is cancer” or “this is normal tissue”).
Each layer takes the output from the previous one and processes it further, getting more detailed understanding as it goes deeper.
CNNs are often used in medical imaging—for example, they can analyze microscope images (digital slides) to help find things like:
dividing cells (mitosis), cell centers (nuclei), or areas where cancer has spread.
In short: a CNN is a system that looks at images, breaks them down into important features, and uses those features to identify what’s in the image.

Question 25

A 29 year old Black woman is evaluated for possible sickle cell disease. She has normal hemoglobin and hematocrit, no evidence of anemia or microcytosis and normal red blood cell indices. Hemoglobin electrophoresis shows fetal hemoglobin (HbF) 30%, HbA1 68.5% and HbA2 1.5%. Family studies show a similar pattern in her father. What is the most likely diagnosis?

Answer 25

Hereditary persistence of fetal hemoglobin (HPFH) is a benign condition with persistent HbF into adulthood, typically asymptomatic, normal red blood cell indices and autosomal dominant inheritance.

Question 26

A 29 year old Black woman is evaluated for possible sickle cell disease. She has normal hemoglobin and hematocrit, no evidence of anemia or microcytosis and normal red blood cell indices. Hemoglobin electrophoresis shows fetal hemoglobin (HbF) 30%, HbA1 68.5% and HbA2 1.5%. Family studies show a similar pattern in her father. Why is the dx not sickle cell disease?

Answer 26

Because sickle cell disease is characterized by HbS on electrophoresis, anemia and vaso-occlusive complications.

Question 27

A 29 year old Black woman is evaluated for possible sickle cell disease. She has normal hemoglobin and hematocrit, no evidence of anemia or microcytosis and normal red blood cell indices. Hemoglobin electrophoresis shows fetal hemoglobin (HbF) 30%, HbA1 68.5% and HbA2 1.5%. Family studies show a similar pattern in her father. Why is the dx not β thalassemia disease?

Answer 27

Because β thalassemia shows microcytosis and elevated HbA2, not isolated HbF elevation.

Question 28

A 29 year old Black woman is evaluated for possible sickle cell disease. She has normal hemoglobin and hematocrit, no evidence of anemia or microcytosis and normal red blood cell indices. Hemoglobin electrophoresis shows fetal hemoglobin (HbF) 30%, HbA1 68.5% and HbA2 1.5%. Family studies show a similar pattern in her father. Why is the dx not δβ thalassemia disease?

Answer 28

Because δβ thalassemia also elevates HbF but is usually associated with microcytosis and mild anemia.

Question 29

Define FISH

Answer 29

🧬 What is FISH? FISH is a lab technique scientists use to find specific DNA sequences inside cells by using glowing (fluorescent) probes. 🔍 Break down the name Fluorescence → gives off light (glows under special light) ✨ In situ → “in place” (inside the cell, not removed) Hybridization → when two matching DNA strands bind together ⚙️ How it works (step by step) Scientists take cells and place them on a slide They make a DNA probe (a short piece of DNA) that matches the sequence they’re looking for They attach a fluorescent dye to the probe The probe is added to the cells If the matching DNA is there, the probe sticks to it Under a special microscope, the spot lights up 🧠 Think of it like this DNA = a long zipper Probe = a small piece of zipper that only fits one spot When it finds the right spot, it zips together and glows, showing where that DNA is. 🧪 What is FISH used for? Scientists and doctors use FISH to: Find specific genes on chromosomes Detect genetic disorders Identify extra or missing chromosomes Study cancer cells 🧬 Example In some diseases, a person might have: An extra copy of a gene Or a missing piece of DNA FISH can show this because: 👉 More copies = more glowing spots 👉 Missing DNA = no glow where it should be 🎯 Simple summary FISH = a method that uses glowing DNA probes to find and locate specific genes inside cells

Question 30

Define PCR?

Answer 30

PCR (Polymerase Chain Reaction) is a method used to make millions of copies of a specific piece of DNA. • It works like a DNA photocopier • It repeats 3 steps: 1. Heat DNA to separate strands 2. Cool so primers attach 3. Build new DNA strands After many cycles → tiny DNA sample becomes easy to study

Question 31

How PCR detects diseases (like COVID-19)

Answer 31

Modern tests use qPCR (quantitative PCR), which: • Copies DNA and detects it at the same time • Uses fluorescent (glowing) markers For COVID: • Virus has RNA → converted to DNA first (RT-PCR) • Then PCR amplifies and detects it ⸻ 💡 What are “glowing markers”? They are fluorescent probes or dyes that light up when DNA is present. Two types: • Dyes: glow when bound to any DNA (less specific) • Probes: glow only when the correct DNA is copied (very specific) 👉 In disease tests, probes are used so only the target (like a virus) triggers light.

Question 32

What does qPCR measure?

Answer 32

qPCR tracks fluorescence over time and makes a graph. Key term: • Ct value (cycle threshold) = when glow becomes detectable - Low CT (15-20) = lots of starting DNA - Medium CT (20-30) = moderate amount - High CT (30-40) = very little DNA Lower Ct = more virus present

Question 33

What does qPCR stand for?

Answer 33

qPCR = quantitative Polymerase Chain Reaction → It measures how much DNA is present, not just yes/no

Question 34

Contrast FISH and qPCR

Answer 34

Fluorescence In Situ Hybridization also uses fluorescence, but works very differently. Main difference: • qPCR → copies DNA and measures how much is there • FISH → does NOT copy DNA, just shows where it is in cells

Question 35

Which of the following is true about the major function of vitamin D? - Increases the absorption of calcium and phosphate from the gastrointestinal tract - Maintenance of normal bone formation, turnover and strength - Raises the circulating calcium concentration while lowering phosphate concentration - Responsible for the regulation of total body phosphate - Stimulates parathyroid hormone synthesis and secretion

Answer 35

Increases the absorption of calcium and phosphate from the gastrointestinal tract. The active form of vitamin D, 1,25(OH)2D, is transported to the small intestine and promotes absorption of calcium and phosphate from the diet.

Question 36

Where in the body is vitamin D converted into 25-hydroxyvitamin D?

Answer 36

Liver. Vitamin D is metabolized to 25(OH)D by 25-hydroxylase in the liver.

Question 37

Explain mass spectrometry

Answer 37

Mass spectrometry sounds complicated, but the idea is actually pretty simple if we break it down. Imagine you have a bunch of tiny LEGO pieces mixed together, and you want to figure out what kinds of pieces are there. Mass spectrometry is like a super-powered tool scientists use to figure out what tiny particles (like molecules) are made of. Here’s how it works in a simple way: 1. Break things into tiny pieces First, the machine takes a sample (like a drop of liquid) and turns it into very tiny charged particles (called ions). Think of this like breaking a LEGO structure into individual pieces and giving each one a little electric charge. 2. Send them flying Next, these charged particles are shot through a machine using electricity or magnets. Because they are charged, they can be pushed and pulled—kind of like how a magnet moves metal. 3. Sort by weight Here’s the cool part: lighter particles move faster, and heavier ones move slower. So the machine separates them based on their mass (how heavy they are). 4. Make a graph Finally, the machine records where the particles land and creates a graph. This graph tells scientists: • what particles are there • how much of each one there is Easy way to remember: Mass spectrometry = break → charge → fly → sort → detect Simple analogy: It’s like a race: • All runners start together • The lighter/faster ones get to the finish line first • The heavier/slower ones arrive later • By watching the results, you figure out who was in the race Scientists use this to: • identify unknown substances • test food and medicine • even study space materials If you want, I can give you a fun real-life example (like how it’s used to detect drugs or proteins). Suppose doctors or police want to know if a person has taken cocaine. They can use mass spectrometry to find out. ⸻ Step-by-step what happens: 1. Take a sample They might take a small sample of blood or urine from the person. ⸻ 2. Turn the drug into charged particles Inside the mass spectrometer, any cocaine in the sample is broken into tiny charged pieces (ions). Think of it like smashing a toy into smaller parts and giving each piece a charge. ⸻ 3. Separate the pieces by mass These charged pieces are sent through the machine. • Lighter pieces move faster • Heavier pieces move slower So the machine spreads them out based on their mass. ⸻ 4. Create a “fingerprint” The machine makes a graph that shows all the pieces and their masses. Here’s the key idea: Every drug breaks apart in a unique way, creating a special pattern—like a fingerprint. Cocaine will always produce the same pattern. ⸻ 5. Compare with known patterns Scientists compare the graph from the sample to known graphs of drugs. If the pattern matches cocaine → they know the drug is present. ⸻ Why this is useful: • It’s very accurate (can detect tiny amounts) • It helps in medical testing, drug laws, and sports doping checks • It can even tell how much of the drug is there ⸻ Simple analogy: It’s like hearing a song on the radio: • Even if you only hear part of it, you can recognize the song • Mass spectrometry “hears” the pieces of a molecule and recognizes the drug

Question 38

Define chromatography

Answer 38

Method in which components of mixture are separated based on their different interactions with a mobile phase and a stationary phase

Question 39

Main function of mobile phase in chromatography

Answer 39

Carry sample component through the chromatography system

Question 40

Where is 25(OH)D is converted to the active form 1,25(OH)2D?

Answer 40

By 1-α-hydroxylase in renal tubular cells