Question

****TYPED PLEASE, NOT HAND WRITTEN*********

****TYPE PLEASE, NOT HAND WRITTEN*********

****TYPE PLEASE, NOT HAND WRITTEN*********

Unit 3 Cases Case connections are short scenarios or puzzles based on the information from the current unit of study. For the Unit 3 Case Connections assignment, you will choose two of the following three case connection problems and provide detailed written solutions To earn full credit, you will need to describe why your chosen answer is correct while also discussing why the other answers are incorrect. Your assignment will be graded on your logic and accuracy as well as on the clarity and organization of the overall assignment. Submit your written assignment via the digital drop box. Case 2: A 53-year-old male with past medical history of obesity (BMI of 38 kg/m2) and borderline diabetes presents to you with abnormal liver enzymes (ALT/AST) discovered 6 months ago. His family history is significant for liver cirrhosis. On physical examination you notice mild hepatomegaly (enlarged liver). A panel of lab tests revealed the following: aspartate aminotransferase (AST) 106 (normal range 10-40 U/L), alanine aminotransferase (ALT) 118 (normal range 7 - 56 U/L), with normal bilirubin (generated from the breakdown of hemoglobin). He had a liver ultrasonography that showed diffuse increase irn echogenicity and vascular blurring consistent with fatty infiltration. You suspect nonalcoholic fatty liver disease (NAFLD). Under normal conditions, describe the metabolism and maturation of VLDL particles. Describe how NAFLD could manifest and what potential processes could be impaired in order for this disease process to occur (consider both enzymatic and hormonal impairments). Case 3 A 20-year old, female presents to the dermatologist with complaints of multiple, small to large (2 mm to 3 cm) soft, asymptomatic yellow colored nodular lesions all over the body since the age of 2 years. She was subsequently referred for biochemical investigations, where an altered lipid profile was noticed A detailed history from the parents revealed that the patient developed the swellings since the age of 2 years, which gradually increased to the present size. At the age of 3 years, patient was treated by a local doctor but the symptoms did not subside. There is no history of chest pain, breathlessness, hypertension, diabetes mellitus, or any other chronic illness. Family history: Maternal side shows history of sudden deaths at a young age (36-44 years) (Mother's elder brother and all his 3 sons have died at an early age due to possible myocardial infarction) Lipid profile of the patient Total cholesterol (mg/dl) 580 Triglycerides (mg/dl) 134 LDL (mg/dI) 460 HDL (mg/dl) 93 VLDL (mg/dI) 27 LDL/HDL ratio 4.94 Please describe a potential underlying mechanism for the elevated cholesterol levels found in this individual. Triglycerides are within normal values in this individual. Describe how triglyceride levels would be normal but cholesterol levels could be elevated in this individual.

Answer 1

Case 2

A. Under normal conditions , the steps of metabolism and maturation of VLDL particles include :-

1- Liver secretes nascent TAG - rich VLDL particles

2- Apo C - ll and apo E are transferred from HDL to nascent VLDL .

3- Extracellular lipoprotein lipase ,activated by apo C -ll , degrades TAG in VLDL

4- Apo C- ll and apo E returned to HDL

5- LDL binds to specific receptors on extrahepatic tissuea and on the liver , where they are endocytosed .

B. Clinical manifestations of Non alcoholic fatty liver disease are :-

- enlarged liver

- fatigue

- pain in upper right abdomen

- ascites

- enlarged blood vessels

- enlarged breaths in men

- enlarged spleen

- red palms

- yellowish colouration of skin and eyes

# Potential factors leading to the disease process to occur are :-

- overweight or obesity

- insulin resistance ,in which the cells don't take sugar in response to the hormone insulin

- high blood sugar indicating pre diabetes or type 2 diabetes mellitus

- high levels of fats , particularly triglycerides in the blood.

CASE 3

The primary diagnosis for this disease is Familial hypercholesterolemia which is a genetic diorder characterized by elevated levels LDL cholesterol, total cholesterol and xanthomas (yellow colored nodules due to cholesterol deposits), this type of conditions classified as type 2 famileal dyslipedemia.

Cholosterol is delivered to the cells through the blood stream, normally the tiny particles of LDL cholesterol attach to receptor sites on the targeted cells and are than absorbed, a gene on chromosome 19 called LDLR gene which controls the production of these receptors, but in most of the cases of hypercholesterolemia is due to the mutation of LDLR gene, which changes the way these receptors work, because of this LDL cholesterol is not well absorbed into the cells and remains circulating in the blood.Some hypercholesterolemia is caused by mutation on other gene like APOB or PCSK9.

In this patient the triglycerides are normal because there is no mutation in the receptor called Liver X receptor which is responsible for the regulation of triglycerides because of this there is less triglycerides circulating in the blood, since the receptor for regulating cholesterol is affected, cholesterol is not fully absorbed in the cell but circulating in the circulatory system.