Reference Tables Or Lookup Tables

I have facing a design problem and unable to justify which design to choose for my data model.

Usually, what we have is like data tables and reference tables to store data in those data tables.
My database has tables with 20-30 columns in them. And most of them (though not all of them), stores data from some reference tables. Meaning each column has an associated reference table where it stores possible list of values for that particular column. Sort of data domain for that column. FYI, My database is related to medical field.

For example, A table that has a varchar(40) column called "Differentiation". It can only store values from following list:
- Undifferentiated
- Moderate
- Poor
- Poor - Moderate
- Moderate - well

Now, to implement this, simple solution would be to have a reference table where I can store all these possible values...And then have just a reference of each data item into my "Differentiation" column in the table.

This is simplest and probably the best solution for such thing and i can also have referential integrity implemented for this.

But now if we look at the bigger picture, my database is growing and I have about 80 tables which I need to create where most of the columns will have different reference tables like I mentioned above. Approximate number of reference tables is 300 tables. All the reference table will have same structure, with different values for different columns.

Now, what seems to me is, because the table structure is same for every column, rather than having 300 different tables, I can only have 2 tables, where I can put all these reference values into these 2 tables.
Like,
Table 1 :
This table can have name of the reference table like "differentiationlist" etc.

Table 2:

It has reference to the reference table list in Table 1 discussed above and all the values that are part of that reference table can go in this table with its reference.

But problem with this is, because all the reference tables are in these two tables, I don't know how to implement referential integrity in this design.

Does anyone have any idea or solution for situation like this?

Thanks,
Ujjaval