Mike Shanahan spent 21 years in Denver – 14 as the head coach. (Toni Sandys / The Washington Post)

The Washington Redskins on Sunday face the mile-high task of defeating Peyton Manning and the Denver Broncos at Sports Authority Field at Mile High at 4:25 p.m. on Fox.

The Redskins enter the game with a 2-4 record while the Broncos are coming off of their first loss of the season.

Washington enters the game as 12.5-point underdogs, but looks to pull off the unexpected and get a win for Mike Shanahan in his return to the city where he won two Super Bowls.

Here are five story lines to follow:

1. Substitute safeties – As Reed Doughty said, “I don’t think it’s ever great timing to face Peyton Manning,” but things have definitely unfolded unfavorably for the Redskins’ secondary  this week. Brandon Meriweather earned a one-game suspension for a pair of helmet-to-helmet hits against the Bears. And Doughty suffered a concussion in the same game, and he has been ruled out for this matchup. Without those two starters, defensive coordinator Jim Haslett must scramble to come up with competent replacements. Rookie Bacarri Rambo has been inactive the past two weeks, but could get a chance to redeem himself after struggling mightily at tackling. Cornerback E.J. Biggers has been used as a safety on passing downs the past couple weeks and likely will hear his number called again this week. Fourth-year veteran Jordan Pugh, first-year player Jose Gumbs and new addition Trenton Robinson also may factor in. But can any of them combine to give the defense a strong backing against the prolific Manning & Co.? Cornerbacks DeAngelo Hall and Josh Wilson have played well, but will they suffer because of the other absences in the secondary?

2. Offensive firepower – The Broncos lead the NFL both in yards gained (469.3) and points scored (42.6) per game. Two of Denver’s receivers rank among the top five in the league in receiving yardage while another two are tied for first in the NFL for touchdown catches. Only once this season have the Broncos scored fewer than 35 points (last week’s 39-33 loss). Washington, meanwhile, ranks fourth in the NFL in yards (415.8 per game), but points have been harder to come by as the Redskins average 25.3. Robert Griffin III & Co. had their most explosive output of the season last week when they scored 45 points in a win over the Bears. A week after going 0 for 3 in the red zone, the Redskins scored four touchdowns inside the 20-yard line. They need similar production this week against Denver, particularly if the defense struggles to slow Manning and his receivers. Denver’s defense is far from invincible, allowing 397 yards (30th) and 28.1 points (27th) game. The Broncos now have top pass rusher Von Miller back, so left tackle Trent Williams must be at his best, and if he can maintain the dominant form he has displayed this season, Washington’s chances for effectiveness increases. The goal remains simple. “We have to score every time we get the ball,” Santana Moss said. Griffin directed a highly effective attack last week as he, Alfred Morris and Roy Helu Jr. combined for 209 rushing yards and the quarterback threw for 298 yards. That type of balance will help the Redskins remain on the field and keep Manning on the sideline.

3. Special teams – The Redskins’ much-maligned special teams units once again will be put to the test. This week’s challenge consists of containing Broncos return man Trindon Holliday, who averages 34.9 yards a kick return and 11.4 yards a punt return. Holliday has both a punt return and kick return for a touchdown. Washington will find it hard enough to keep Denver’s offense off the board, so they can’t afford to give up special teams touchdowns as they have in each of the past three games. Field position will likely winding up factoring into this game. The Redskins want to put the Broncos offense in as many unfavorable situations as possible. Meanwhile, Washington’s stagnant returns units have to perform better and help out their own offense by giving Griffin and his crew shorter fields to work with.

4. Wily veterans – This game features two of the most respected field generals in the game as 16-year veterans Peyton Manning and London Fletcher face off against one another. Manning is known for his ability to read defenses, distinguish their intentions and then make the pre-snap adjustments to exploit weaknesses. Fletcher, meanwhile, has a reputation of being a coach on the field as he reads offenses, puts his teammates in the proper position to make plays and racks up tackles as well. “It’s us old graybeards out there,” Fletcher said of the matchup, which he expects will be like a chess match. Fletcher’s seven-man defensive front must put as much pressure on Manning as possible to keep the future Hall of Fame quarterback from carving their secondary up. But they can’t tip their hand pre-snap. Timing and effectiveness will prove crucial. The Redskins also have to be sound against the run, because if they’re so focused on the pass that they leave gaps open for Knowshon Moreno, who leads the NFL with eight rushing touchdowns, it will make for a long day.

5. Shanahan’s return – It’s been four years since he was fired as head coach of the Broncos, but this marks the first time Mike Shanahan will coach against his former team. Shanahan acknowledges that he has fond memories of his 21 years in Denver (14 as head coach) and the two Super Bowls he won there. But he says he has no greater motivation to win this game than any other game. With the Redskins in a desperate situation at 2-4, it doesn’t matter who they’re playing, the coach says. But his son and offensive coordinator, Kyle Shanahan, suspects that beating Denver would indeed be special to the head coach. “You always want to beat people that you used to work for,” Kyle Shanahan says. The Broncos will honor Mike Shanahan with a video tribute, and he will see plenty of old friends, and it could make for an emotional day. Will Shanahan leave his old stomping ground on a joyous note, or in disappointment?

Have a Redskins question? E-mail Mike Jones at mike.jones@washpost.com with the subject line “Mailbag question” for him to answer it in The Mailbag on Tuesdays.

What’s ahead:

● The Redskins have their final practice before leaving for Denver. Sunday’s game is at 4:25 p.m.

More on the Redskins and NFL:

Redskins aim to face Broncos with patchwork secondary

Shanahan and Davis have talked ‘responsibilities’ | Hankerson aims to play

D.C. Sports Bog: Marshall and Meriweather exchanged text messages | More

Haslett confident in remaining safeties | Must teach Meriweather better tackling

Thursday night: Panthers manhandle Buccaneeers

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